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This research aimed to investigate the biological properties of different hydrolysates derived from industrial and laboratory defatted rice bran proteins. Industrial and laboratory defatted rice bran protein concentrates were hydrolyzed with alcalase or flavorzyme. The degree of hydrolysis (DH), oxygen radical absorbance capacity (ORAC), reducing power, total phenolic compounds (TPC), and angiotensin-converting enzyme (ACE) inhibitory activity, were determined in the hydrolysates and the molecular fractions lower than 3 kDa. Systolic blood pressure (SBP) was measured using the tail-cuff method before and after oral administration of 80 mg/kg of different rice bran protein hydrolysate (RBPH) fractions lower than 3 kDa in male spontaneously hypertensive rats (SHR) and normotensive Wistar&ndash, Kyoto (WKY) rats. The highest values of in vitro antioxidant activity and TPC were observed in RBPH with alcalase defatted by industry (RBPH2A), and, in all cases, these bioactivities were higher in the molecular fractions lower than 3 kDa. Once again, fractions lower than 3 kDa obtained with alcalase showed a potent ACE inhibitory activity (RBPH1A&lt, 3 and RBPH2A&lt, 3). The administration of RBPH1A&lt, 3 caused a significant decrease in the SBP in SHR, where the maximum decrease was reached at 8 h after administration. SBP in WKY rats was not modified after the administration of RBPH1A&lt, 3. These results suggest that the rice bran protein hydrolysates obtained from industry after treatment with alcalase could be an interesting source of bioactive peptides, with potential action on hypertension and other related pathologies.

We evaluated the effect of oral administration of Bifidobacterium animalis subsp. lactis CECT 8145 strain in Zücker fatty rats. The Zücker fatty rats were randomly divided into two groups (n=10 each) and administered either B. animalis subsp. lactis CECT 8145 (1010 cfu/day) suspended in skim milk, or skim milk alone (control group). Each treatment was administered in drinking bottles from week 5 until week 17 of age. A lean Zücker rat group (standard group) was included to provide normal values for the Zücker strain. This group was administered skim milk in the drinking bottle for the same experimental period as Zücker fatty rats. Body weight gain was greater in the fatty control group than in the fatty rats treated daily with B. animalis subsp. lactis CECT 8145. Furthermore, dry and liquid food intake significantly decreased in the treated Zücker fatty group and these rats also showed decreased plasma ghrelin levels as compared with the Zücker fatty control group. B. animalis subsp. lactis CECT 8145 intake also decreased plasma tumour necrosis factor-α (a proinflammatory cytokine) and plasma malondialdehyde (a biomarker of oxidative stress). Moreover, the ratio plasma total cholesterol/plasma cholesterol transported by high-density lipoproteins, considered as an index for cardiovascular disease, also significantly decreased in the Zücker fatty rats treated with B. animalis subsp. lactis CECT 8145. By contrast, this bacterial strain significantly increased plasma adiponectin (an insulin-sensitising adipokine), but did not produce significant effects on triglyceride levels or glucose metabolism biomarkers. Although further research is required to confirm B. animalis subsp. lactis CECT 8145 is an efficient anti-obesity treatment in humans, the results obtained in this study are promising and point to the health and anti-obesity properties of this bacterial strain.

Recently, microbial changes in the human gut have been proposed as a possible cause of obesity. Therefore, modulation of microbiota through probiotic supplements is of great interest to support obesity therapeutics. The present study examines the functional effect and metabolic targets of a bacterial strain, Bifidobacterium animalis subsp. lactis CECT 8145, selected from a screening in Caenorhabditis elegans. This strain significantly reduced total lipids (40.5% ± 2.4) and triglycerides (27.6% ± 0.5), exerting antioxidant effects in the nematode (30% ± 2.8 increase in survival vs control); activities were also preserved in a final food matrix (milk). Furthermore, transcriptomic and metabolomic analyses in nematodes fed with strain CECT 8145 revealed modulation of the energy and lipid metabolism, as well as the tryptophan metabolism (satiety), as the main metabolic targets of the probiotic. In conclusion, our study describes for the first time a new B. animalis subsp. lactis strain, CECT 8145, as a promising probiotic for obesity disorders. Furthermore, the data support future studies in obesity murine models.

AVFQHNCQE is an antihypertensive nonapeptide obtained from a chicken foot protein hydrolysate. The present study aims to investigate the mechanisms involved in its blood pressure (BP)-lowering effect. Male (17&ndash, 20 weeks old) spontaneously hypertensive rats (SHR) were used in this study. Rats were divided into two groups and orally administered water or 10 mg/kg body weight (bw) AVFQHNCQE. One hour post-administration, animals of both groups were intra-peritoneally treated with 1 mL of saline or with 1 mL of saline containing 30 mg/kg bw N&omega, nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, or with 1 mL of saline containing 5 mg/kg bw indomethacin, which is an inhibitor of prostacyclin synthesis (n = 6 per group). Systolic BP was recorded before oral administration and six hours after oral administration. In an additional experiment, SHR were administered water or 10 mg/kg bw AVFQHNCQE (n = 6 per group) and sacrificed six hours post-administration to study the mechanisms underlying the peptide anti-hypertensive effect. Moreover, the relaxation caused by AVFQHNCQE in isolated aortic rings from Sprague-Dawley rats was evaluated. The BP-lowering effect of the peptide was not changed after indomethacin administration but was completely abolished by L-NAME, which demonstrates that its anti-hypertensive effect is mediated by changes in endothelium-derived NO availability. In addition, AVFQHNCQE administration downregulated aortic gene expression of the vasoconstrictor factor endothelin-1 and the endothelial major free radical producer NADPH. Moreover, while no changes in plasma ACE activity were observed after its administration, liver GSH levels were higher in the peptide-treated group than in the water group, which demonstrates that AVFQHNCQE presents antioxidant properties.

The antihypertensive properties of different doses of a chicken foot hydrolysate, Hpp11 and the mechanisms involved in this effect were investigated. Spontaneously hypertensive rats (SHR) were administered water, Captopril (50 mg/kg) or Hpp11 at different doses (25, 55 and 85 mg/kg), and the systolic blood pressure (SBP) was recorded. The SBP of normotensive Wistar-Kyoto (WKY) rats administered water or Hpp11 was also recorded. Additionally, plasmatic angiotensin-converting enzyme (ACE) activity was determined in the SHR administered Hpp11. Moreover, the relaxation caused by Hpp11 in isolated aortic rings from Sprague-Dawley rats was evaluated. Hpp11 exhibited antihypertensive activity at doses of 55 and 85 mg/kg, with maximum activity 6 h post-administration. At this time, no differences were found between these doses and Captopril. Initial SBP values of 55 and 85 mg/kg were recovered 24 or 8 h post-administration, respectively, 55 mg/kg being the most effective dose. At this dose, a reduction in the plasmatic ACE activity in the SHR was found. However, Hpp11 did not relax the aortic ring preparations. Therefore, ACE inhibition could be the mechanism underlying Hpp11 antihypertensive effect. Remarkably, Hpp11 did not modify SBP in WKY rats, showing that the decreased SBP effect is specific to the hypertensive state.

Three citrus fruit extracts (orange, grapefruit and lemon), an olive leaf extract and a citrus–olive mixed extract (Citrolive), which was obtained from olive leaf and bitter orange fruits, were characterized by HPLC and investigated for their endothelium-dependent vascular relaxing ability. Subsequently, aorta rings from SHR were mounted in tissue baths. They were pre-contracted with methoxamine and exposed to the extracts. Intact, endothelium-denuded, L-NAME-, indomethacin- and sirtinol-treated preparations were used. All extracts exhibited endothelium-dependent relaxations that were totally reversed by L-NAME and partly blocked by sirtinol. Indomethacin also decreased the relaxing effect of high doses of lemon and olive extracts, but the arterial relaxations caused by low doses of the different extracts and those caused by high doses of Citrolive extract (a mixed extract) were potentiated by indomethacin. This study confirms Mediterranean plants as an excellent source of functional compounds, showing the relaxing effect of the assayed plant extracts in aorta rings from SHR. Moreover, the results obtained demonstrate the endothelium-dependent vascular relaxing effect of the studied extracts. Endothelial NO release seems implicated in the effect of all extracts and prostacyclin probably participates in the effect of lemon and olive extracts. Nevertheless, enhanced vasoconstrictor endoperoxides seem to be of special importance in the endothelial tissue of SHR, and the release of these products may impair, at least in part, the endothelium-dependent vascular relaxation caused in these animals by orange, grapefruit, lemon, olive, and in particular, Citrolive extracts.

10.1016/j.jff.2013.11.008 The aim of this study was to evaluate the involvement of endothelial-relaxing factors as possible antihypertensive mechanism of low-molecular-weight procyanidin rich grape seed extract (LM-GSPE). Thirty 17¿20-week-old male spontaneously hypertensive rats (SHR) were administered water or 375 mg/kg LM-GSPE by intragastric gavage. One millilitre of saline, 30 mg/kg NG-Nitro-L-arginine methyl ester (L-NAME) or 5 mg/kg indomethacin was administrated intraperitoneally. Systolic blood pressure (SBP) and diastolic blood pres- sure (DBP) were recorded before and 6 h after oral administration. Plasma concentration of 6-keto-prostaglandin F1a (PGF1a) was quantified. In addition, we evaluated the relaxation caused by LM-GSPE in different aorta preparations. The antihypertensive effect of LM-GSPE was completely and partially abolished by L-NAME and indomethacin, respectively. In addi- tion, plasma PGF1a was increased in LM-GSPE-administered rats. Finally, LM-GSPE relaxed the intact aorta preparations but did not relax the endothelium-denuded aorta rings. L- NAME inhibited the relaxation caused by LM-GSPE in the SHR aorta rings, but indometha- cin did not. Therefore, the antihypertensive effect of LM-GSPE in SHR is endothelium dependent, and it could be mediated by changes in endothelium-derived nitric oxide bio- availability. Nevertheless, prostacyclin could also contribute additionally to this effect.

This is an open access article distributed under the Creative Commons Attribution License., The effect of long-term intake of different doses (20, 40, and 60 mg/kg/day) of a Fraxinus excelsior L. seed extract (FESE) on spontaneously hypertensive rats (SHR) was evaluated. Water was used as control and captopril (50 mg/kg/day) was used as positive control. Systolic blood pressure, body weight, and food and liquid intake were registered weekly in SHR. The antioxidant and vascular relaxing properties of FESE were also studied in these animals. The development of hypertension was attenuated in the groups treated with captopril or FESE. The antihypertensive effect was more accentuated in the captopril group than in the FESE groups, and it was paradoxically more accentuated in the groups treated with 20 mg/kg/day or 40 mg/kg/day of FESE than in the group treated with the highest dose of this extract. Body weight gain and food intake increased in the FESE groups. After removing the corresponding antihypertensive treatment, the arterial blood pressure and the body weight of the FESE treated animals returned to control values. In addition, FESE increased plasma antioxidant capacity and decreased plasma and liver malondialdehyde levels. Moreover, acetylcholine relaxation improved in the aorta rings from the FESE treated rats. © 2014 Noemi López-Carreras et al.

Grapes are a good source of flavonoids, which have been previously demonstrated to exert beneficial healthy effects on cardiovascular diseases. The aims of this study were to extensively characterise a grape seed procyanidin extract (GSPE) (total phenolic content, antioxidant capacity and HPLC–MS phenolic profile) and, to assess its antihypertensive effect in spontaneously hypertensive rats (SHR) which is a model of genetically hypertensive rat analogue to the essential hypertension in humans. The hypotensive effect of GSPE was also proved in normotensive Wistar–Kyoto rats. Chromatographic analysis of the extract showed that the most abundant polyphenols are monomers and dimers, in their free forms and linked to a gallate. GSPE produced a significant decrease in systolic and diastolic blood pressure of SHR dose-dependently up to 375 mg/kg (maximum decrease 6 h post-administration) and did not affect blood pressure of Wistar–Kyoto rats. GSPE increased the activity of an antioxidant endogen system, but did not affect plasma ACE activity in these animals.

[Background and Methods]: This study evaluates the antihypertensive effect of long-term intake of a soluble cocoa fiber product (SCFP). Different doses of SCFP were evaluated (200, 400, and 800 mg/kg/day) and a dose of 800 mg/kg/day of beta-glucan 0.75 (BETA-G) was used as a standard fiber. Water, a neutral vehicle, was used as negative control, and 50 mg/kg/day captopril was used as positive control. Systolic blood pressure (SBP) was measured weekly by the tail cuff method. Body weight, food, and liquid intake were also registered weekly in the rats from 10 to 24 weeks of life. Glucose, total cholesterol, and triglyceride levels; redox status; and the angiotensin-converting enzyme activity were also studied in the plasma samples of these animals. [Results]: Throughout the 10 weeks of treatment, captopril and SCFP (400 mg/kg/day) demonstrated blood pressure lowering effects in the spontaneously hypertensive rats (pB0.05; n8). Paradoxically, neither the highest dose (800 mg/kg/day) of SCFP decreased SBP nor 800 mg/kg/day BETA-G (p0.05; n8). When the corresponding antihypertensive treatment, was disrupted the SBP values of the 400 mg/kg/day SCFP treated animals returned to control values (p0.05; n8). In addition, the SCFP significantly decreased (pB0.05; n4) the glucose, cholesterol, and triglyceride levels and also the liver and plasma malondaldehyde levels. Moreover, the SCFP slightly increased the reduced glutathione levels in the liver. [Conclusion]: The SCFP could be used to control the blood pressure of hypertensive subjects for a long period of time and could improve metabolic complications associated to cardiovascular diseases., This study was supported by UCM project (206/2006) MINECO, AGL2012-32387 and Intramural CSIC, 201570Io28.

8 páginas, 5 figuras, 2 tablas., The effects of a soluble cocoa fiber (SCF) were studied in Zucker fatty rats. Two groups of Zucker fatty rats were fed the following diets: standard diet and 5% SCF-enriched diet. A group of Zucker lean rats fed the standard diet was used for results comparison with obese Zucker animals. Solid and liquid intakes, body weight, plasma glucose, lipid profile, and systolic (SBP) and diastolic (DBP) blood pressure were recorded weekly. At the end of the experimental period insulin was determined, and fat apparent digestibility (FAD) and insulin resistance were calculated. The Zucker fatty rats fed 5% SCF-enriched diet showed less weight gain and food intake than those fed the standard diet. The group fed the fiber-enriched diet showed lower values of the total cholesterol/high-density lipoprotein cholesterol ratio and triglyceride levels than the standard group. FAD was also lower in the fiber group. Both SBP and DBP were decreased. In addition, SCF reduced plasma glucose and insulin, and as a consequence the insulin resistance was also decreased. Our data demonstrate that SCF resulted in an improvement of the studied risk factors associated with cardiometabolic disorders., This study was supported by Natraceutical Group (206= 2006 U.C.M. Project). M.M. is the recipient of a Ramon y Cajal contract from MICINN.

Being the metabolic syndrome a multifactorial condition, it is difficult to find adequate experimental models to study this pathology. The obese Zucker rats, which are homozygous for thefaallele, present abnormalities similar to those seen in human metabolic syndrome and are a widely extended model of insulin resistance. The usefulness of these rats as a model of non-insulin-dependent diabetes mellitus is nevertheless questionable, and they neither can be considered a clear experimental model of hypertension. Some experimental models different from the obese Zucker rats have also been used to study the metabolic syndrome. Some derive from the spontaneously hypertensive rats (SHR). In this context, the most important are the obese SHR, usually named Koletsky rats. Hyperinsulinism, associated with either normal or slightly elevated levels of blood glucose, is present in these animals, but SHR/N-corpulent rats are a more appropriated model of non-insulin-dependent diabetes mellitus. The SHR/NDmc corpulent rats, a subline of SHR/N-corpulent rats, also exhibit metabolic and histopathologic characteristics associated with human metabolic disorders. A new animal model of the metabolic syndrome, stroke-prone–SHR (SHRSP) fatty rats, was obtained by introducing a segment of the mutant leptin receptor gene from the Zucker line heterozygous for thefagene mutation into the genetic background of the SHRSP. Very recently, it has been developed as a non-obese rat model with hypertension, fatty liver and characteristics of the metabolic syndrome by transgenic overexpression of a sterol-regulatory element-binding protein in the SHR rats. The Wistar Ottawa Karlsburg W rats are also a new strain that develops a nearly complete metabolic syndrome. Moreover, a new experimental model of low-capacity runner rats has also been developed with elevated blood pressure levels together with the other hallmarks of the metabolic syndrome.

The aim of this study was to investigate the potential angiotensin converting enzyme (ACE)-inhibitory activity and the antihypertensive effect, after a single oral administration, of a pepsin hydrolysed bovine casein (HBC) and a fraction with molecular mass lower than 3000 Da (HBC < 3000). ACE-inhibitory activity was measured by spectrophotometric assay. These products were orally administered by gastric intubation. The systolic (SBP) and the diastolic blood pressure (DBP) were measured in spontaneously hypertensive rats by the tail cuff method before administration and also 2, 4, 6, 8, and 24 h post-administration. HBC showed a potent ACE-inhibitory activity. This activity was 10 times higher in HBC < 3000. HBC and HBC < 3000 decreased the arterial blood pressure of the rats. The decrease in the SBP observed for HBC (400 mg/kg) or HBC < 3000 (200 mg/kg) was less pronounced than that caused by 50 mg/kg of captopril (antihypertensive positive control). However, the maximal decreases in DBP caused by HBC or HBC < 3000 were as high as the maximum decrease observed for captopril. The antihypertensive effect of these products was transient and reverted 24 h after the administration. HBC and HBC < 3000 exert antihypertensive effect caused by small peptides with ACE-inhibitory activity.

This paper examines the effects of the long-term consumption of egg white hydrolysed with pepsin (hEW) on the antioxidant status and lipid profile of spontaneously hypertensive rats (SHR). The antioxidant capacity was measured by the oxygen radical absorbance capacity (ORAC) and the oxidative status by the malon-dialdehyde (MDA) assay. The lipid profile was analysed spectrophotometrically. The radical-scavenging capacity of the plasma was increased and the MDA concentration in the aorta was decreased in the SHR treated with 0.5 g/kg/day of hEW. Our findings indicate that hEW played an important role in antioxidative defence of SHR and exerted a beneficial effect on the lipid profile, lowering triglycerides and total cholesterol without changing HDL levels. Therefore, hEW may be useful to prevent or reverse abnormalities associated with the metabolic syndrome and its complications, such as hypertension, oxidative stress and hyperlipidemia.

Las ratas Zucker obesas son el modelo animal mejor conocido de obesidad genetica. La obesidad en estos animales se hereda como caracter autosomico recesivo. Las ratas afectadas presentan una mutacion en el receptor de leptina y acusan hiperfagia y otras alteraciones semejantes a las que aparecen en el sindrome metabolico humano. Estos animales presentan hiperinsulinemia, por lo que se los puede considerar tambien un modelo de resistencia a la insulina. Su utilidad como modelo de diabetes mellitus tipo 2, sin embargo, es cuestionable, pues presentan solo ligera intolerancia a la glucosa. El perfil lipidico de estos animales tambien esta alterado. Hay aumento de lipoproteinas de muy baja densidad (VLDL) y de alta densidad (HDL), pero no aumenta el colesterol de las lipoproteinas de baja densidad y no se los puede utilizar como modelo de aterogenesis. Tampoco se los considera un modelo de hipertension, aunque pueden presentar valores altos de presion arterial sistolica a partir de las 28 semanas de vida.

In this study, we evaluated the effect of a highly methoxylated apple pectin (HMAP) on cardiometabolic risk factors in Zucker fatty rats. beta-Glucan, a fiber known for its hypocholesterolemic properties, also was used. The rats fed both fiber-enriched diets exhibited a reduction in body weight and in total cholesterol and triglycerides when compared to the Zucker fatty rats fed the standard diet. The effect on the lipid profile was more remarkable in the HMAP group. A decrease in blood glucose was only noticed in this group. Moreover, a decrease in plasma insulin, HOMA-IR, and HOMA-beta was noticed in the fiber groups, and in particular in the HMAP group, these variables being similar to the lean rats. Blood pressure and endothelial function were similar in all the Zucker fatty rats. These results warrant evaluation in humans to determine if HMAP could be used as a functional ingredient to reduce lipid profile, insulin resistance, and other cardiometabolic risk factors.

This paper evaluates the effects of the short- (1 g/kg) and long-term (0.5 and 1 g/kg/day) oral intake of egg white hydrolysed with pepsin (hEW) and the long-term oral intake (1 g/kg/day) of egg white (EW) on local angiotensin-converting enzyme (ACE) activities in plasma and other tissues of spontaneously hypertensive rats (SHR), as compared to the effect of the ACE inhibitor prototype captopril. The rats treated with hEW were classed in a different group than the control rats and the rats treated with EW by cluster analysis, taking into account their tissue ACE activities and their systolic blood pressure (SBP). Principal component analysis (PCA) showed that SBP in SHR was negatively related with ACE activity in plasma and positively related with ACE activity in aorta and kidney. ACE activity in plasma significantly increased after the long-term treatment with hEW (0.5 g/kg/day). ACE activity in aorta and kidney was significantly inhibited 4 h after the short-term administration of hEW. The long-term treatment with hEW caused local effects on ACE activity in aorta, kidney and lungs that followed a pattern similar, but less pronounced, than that caused by captopril.

In previous studies we showed that the egg white hydrolysate with pepsin (HEW) and its fraction with molecular mass lower than 3000 Da (HEW

Several novel peptides with demonstrated antihypertensive activity have been identified in milk fermented with Enterococcus faecalis CECT 5727. Two of the identified peptides, corresponding to β-casein f(133–138) (LHLPLP) and β-casein f(58–76) (LVYPFPGPIPNSLPQNIPP), showed angiotensin converting enzyme-inhibitory (ACEI) activity (IC50) values as low as 5 μm. These peptides demonstrated antihypertensive activity when they were orally administered to spontaneously hypertensive rats. In particular, β-casein f(133–138), yielded a significant antihypertensive effect in these animals. The maximal decreases in systolic blood pressure (21.87±4.51 mmHg, ) and diastolic blood pressure (28.5±3.20 mmHg, ) were observed 4 and 2 h, respectively, after the administration of 2 mg kg−1 of this peptide. The presence of these antihypertensive peptides in fermented milk prepared with other selected strains of E. faecalis (CECT 5728, 5826 and 5827) was confirmed by HPLC-MS., This work has received financial support from the projects AGL2004-06903-C02-01 and FIT-06000-2002-30. A. Quirós was the recipient of a fellowship of the I3P Programme from the Consejo Superior de Investigaciones Científicas.

7 pages., [Introducción y objetivos] La fermentación de la leche por algunas bacterias genera péptidos con actividad inhibidora de la enzima convertidora de la angiotensina. Se evalúan los cambios de la presión arterial que produce en ratas espontáneamente hipertensas la administración crónica de leche fermentada por Enterococcus faecalis CECT 5728 con actividad inhibidora de esta enzima., [Material y métodos] Se utilizaron ratas macho espontáneamente hipertensas recién destetadas con 3 semanas de vida. Las ratas se dividieron en cinco grupos que ingerían los siguientes productos líquidos: agua (control negativo), leche fermentada sin actividad inhibidora de la enzima convertidora de la angiotensina (testigo), captopril (100 mg/kg) (control positivo), leche fermentada por Enterococcus faecalis CECT 5728 y leche fermentada por Enterococcus faecalis CECT 5728 que estaba enriquecida en calcio. Los tratamientos se retiraron cuando las ratas tenían 20 semanas de vida. Se midió la presión arterial sistólica y diastólica de las ratas mediante el método del maguito en la cola cuando tenían 5, 10, 15, 20 y 25 semanas de vida., [Resultados] El tratamiento con captopril disminuyó significativamente la presión arterial sistólica y diastólica de las ratas. La leche fermentada por Enterococcus faecalis CECT 5728 también disminuyó significativamente estas variables, pero su efecto fue menor que el de captopril. Los valores de la presión arterial sistólica y diastólica aumentaron tras la retirada de los tratamientos antihipertensivos., [Conclusiones] Podría utilizarse la cepa bacteriana Enterococcus faecalis CECT 5728 para producir leches fermentadas útiles en el tratamiento y/o la prevención de la hipertensión., [Introduction and objectives] Fermentation of milk by some bacteria generates peptides with angiotensin converting enzyme inhibitor activity. The changes of blood pressure that are produced in spontaneous hypertensive rats by the chronic administration of milk fermented by Enterococcus faecalis CECT 5728 with inhibitor activity of this enzyme are evaluated., [Material and methods] Recently weaned spontaneous male hypertensive rats with 3 weeks of life were used.The rats were divided into five groups that took the following liquid products: water (negative control), fermented milk without angiotensin converting enzyme inhibitor activity (control), captopril (100 mg/kg) (positive control), milk fermented by Enterococcus faecalis CECT 5728, and milk fermented by Enterococcus faecalis CECT 5728 that was enriched in calcium. The treatments were withdrawn when the rats were 20 weeks old. Systolic and diastolic blood pressure of the rats was measured with the tail cuff method, when they were 5, 10, 15, 20 and 25 weeks old., [Results] Treatment with captopril significantly decreased the systolic and diastolic blood pressure of the rats. Milk fermented by Enterococcus faecalis CECT 5728 also significantly decreased these variables, but its effect was less than that of captopril. The systolic and diastolic blood pressure values increased after withdrawal of the antihypertensive treatments., [Conclusions] The bacterial strain Enterococcus faecalis CECT 5728 can be used to produce fermented milks useful in the treatment and/or prevention of hypertension., Financiado por el grupo Leche Pascual, S.A., y por el proyecto INIA-MCYT (CAL01-046-02).

It has been suggested that the combination of dietary Ca and Ca 2+ channel antagonists could have a synergic antihypertensive effect. In this study, 3-week-old male spontaneously hypertensive rats (SHR) were randomized into four groups of animals. Two of these groups were fed on a normal Ca diet (Ca 1%) and the other two groups were fed on a Ca-enriched diet (Ca 2.5%). One of the groups fed on each diet also received amlodipine (1 mg/kg/day) in their drinking water. Systolic and diastolic arterial blood pressure were measured weekly in the rats, from the 6th week of life until the 25th week of life, by the tail-cuff method, and we also calculated the corresponding pulse pressure values (systolic blood pressure−diastolic blood pressure). Determination of plasma Ca levels by colourimetric methods, and measurement in pithed rats of the pressor responses to the α-adrenoceptor agonists methoxamine and B-HT 920 (5-allyl-2-amino-5,6,7,8-tetrahydro-4 H -thiazolo-(4,5- d )-acepin-dihydrochloride, talixepole) were also performed using 16- and 23-week-old animals from the different groups. The Ca-enriched diet decreased systolic and diastolic blood pressure in SHR. Almodipine also decreased systolic and diastolic blood pressure in SHR, and this drug intensified the antihypertensive effect of the Ca 2.5% diet in the SHR between weeks 13 and 18. Nevertheless, in the 19- to 25-week-old SHR amlodipine antagonized the effect of dietary Ca on arterial blood pressure. A decrease in the pulse pressure was seen only in the 15- to 20-week-old SHR which had been simultaneously treated with dietary Ca and amlodipine. All the treatments used increased calcaemia, and the highest plasma Ca levels were obtained in the animals which had received the combined treatment with Ca and amlodipine. The responses to methoxamine and to B-HT 920 in the pithed 16-week-old SHR were similar in the four groups of animals. The responses to these agonists in the pithed 23-week-old SHR fed on the Ca-enriched diet were smaller than the corresponding responses in 23-week-old SHR of the untreated group. By contrast, the responses to these agonists were slightly higher in the pithed 23-week-old SHR which were treated with amlodipine than in the pithed 23-week-old SHR in the untreated group. Moreover, amlodipine partially reversed the effect of dietary Ca on α-vascular reactivity. According to our results, it would seem inadvisable to use dietary Ca with a Ca 2+ channel antagonist with the aim of controlling arterial blood pressure.

The present study was designed to prove whether the activation of the sarcolemmal Na+/K+-ATPase in the rabbit aorta could explain the decreased contraction caused in this tissue by high extracellular calcium. To demonstrate this hypothesis, we evaluate the modification in the contractile responses to KCl and alpha1-adrenoceptor agonists (methoxamine and phenylephrine) produced by a high extracellular Ca2+ concentration (10 mM) in isolated rabbit aorta rings when the Na+/K+-ATPase is inhibited with ouabain. Ouabain 10(-4) M caused an initial rapid increase in tone in the rabbit aorta rings, which could be linked to the release of catecholamines provoked when the Na+/K+-ATPase in the nerve terminal was blocked. This glycoside also caused a delayed contractile response in the preparations that could be linked to the inhibition of the Na+/K+-ATPase in the sarcolemma of the smooth muscle. The maximum inhibition of the sarcolemmal pump was fixed 2 h and 15 min after ouabain 10(-4) M administration. Both responses were smaller with the 10-mM Ca2+ concentration than with the 2.5-mM Ca2+ concentration. The contractions elicited by KCl and the alpha1-adrenoceptor agonists were higher in the aorta ring preparations incubated with the 2.5-mM Ca2+ solution than in the aorta ring preparations incubated with the 10-mM Ca2+ solution. When the Ca2+ concentration in the organ bath was 2.5 mM, 10(-4) M ouabain administration caused a decrease in the responses to KCl and alpha1-adrenoceptor agonists. By contrast, when the Ca2+ concentration in the organ bath was 10 mM, 10(-4) M ouabain did not modify these responses. As a consequence, the contractions elicited by KCl were very similar in all the ouabain-treated preparations and those elicited by the alpha1-adrenoceptor agonists in ouabain-treated preparations were even higher when the Ca2+ concentration in the organ bath was 10 mM than when the Ca2+ concentration in the organ bath was 2.5 mM. The results of this study suggest that the increase in extracellular Ca2+ concentration may facilitate the functioning of the Na+/K+-ATPase in the vascular smooth muscle (VSM) and produces opposite effects to ouabain. This effect of high extracellular Ca2+ concentration on the sarcolemmal pump may explain the decrease in the contractile responses elicited by depolarization and alpha1-adrenoceptor stimulation observed in rabbit aorta ring preparations.

We studied the short-term antihypertensive effect of flavan-3-ols (-)-epicatechin, (+)-catechin and (-)-catechin, in spontaneously hypertensive rats (SHR). Plasma metabolites and the corresponding plasma antioxidant capacity were determined. All the assayed flavan-3-ols decreased systolic blood pressure (SBP) in SHR. Their antihypertensive effects were less pronounced than that of Captopril (50 mg kg) and were not shown in normotensive Wistar-Kyoto rats. 6 mg kg (-)-epicatechin caused the maximum decrease in SBP. The maximum effects of the catechin monomers were observed post-administration of 0.5 mg kg of flavan-3-ols, (-)-catechin being the least effective among the three assayed compounds. Glucuronide and methyl glucuronide metabolites were obtained in the flavan-3-ol treated SHR, but it was not possible to relate the antihypertensive effect of the assayed flavan-3-ols with a concrete plasma metabolite or with their antioxidant effect. In conclusion, the studied flavan-3-ols could be responsible for the antihypertensive effect of cocoa products., This study was supported by Natraceutical Group (36/2007 U. C.M. Project) and for the Spanish Government (AGL2013-40707-R). M.Q. is a recipient of a Postdoctoral fellowship from Galician Government (Xunta de Galicia ED481B2014/039-0).

The release of endothelial relaxing factors has been suggested to be important in modulating the inhibition of the contractile activity caused by the increase in extracellular Ca 2+ concentration in arterial tissue. Since the hypertensive process in spontaneously hypertensive rats (SHR) could be associated with the release of endothelial vasoconstrictor factors (mainly cyclooxygenase-dependent endoperoxides and endothelin-1), we studied the contractile responses to KCl, methoxamine and phenylephrine in different aorta ring preparations (intact, de-endothelized, 10 −5 M indomethacin-treated, 10 −6 M CGS-27830 [meso-1,4-dihydro-5-methoxycarbonyl-2, 6-dimethyl-4-(3-nitrophenyl)-3-pyridine carboxylic acid anhydride]-treated, and treated simultaneously with 10 −5 M indomethacin and 10 −6 M CGS-27830) from SHR and normotensive Wistar Kyoto rats (WKY), at various Ca 2+ concentrations (1.25, 2.5, 5 and 10 mM) in the organ bath. In endothelium-intact preparations from WKY rats we observed a decrease in KCl, methoxamine and phenylephrine contractions with high Ca 2+ concentrations (5 and 10 mM), but in the endothelium-intact preparations from SHR, the increase in extracellular Ca 2+ concentration potentiated methoxamine contractions and caused no change in KCl and phenylephrine contractions. When the endothelium was disrupted in preparations from both WKY rats and SHR, we observed a decrease in KCl and methoxamine contractions with high Ca 2+ concentrations. The decrease in phenylephrine contractions caused by high Ca 2+ concentrations was clear in de-endothelized preparations from WKY rats but slight in de-endothelized preparations from SHR. In all indomethacin- and CGS-27830-treated preparations, and also in the preparations from WKY rats and SHR treated with both drugs, we observed a decrease in all the contractile responses with increased Ca 2+ concentration. Besides, there was a clear reduction in the responses of the α 1 -adrenoceptor agonists in the WKY and SHR preparations treated with both drugs. The results indicate that, in the hypertensive arteries, endothelium-derived contractile factors can counteract the relaxing effect of high extracellular Ca 2+ concentrations.

A change in endothelial function is a common phenomenon in patients with essential hypertension and in animals with hypertension, whether primary or induced by a salt-rich diet. In hypertensive subjects, there may be a change in the synthesis, or the effect, of nitric oxide. Nevertheless, hypertensive vasoconstriction is at present associated, above all, with the degradation of this mediator by free radicals, such as the superoxide anion, released in the dysfunctional vascular endothelium. These radicals are also formed when hypoxanthine is turned into xanthine, and when the latter becomes uric acid, both having been catalysed by the enzyme xanthine oxidase. In physiological conditions, the concentration of superoxide radicals remains low within the organism as a result of its reaction with the superoxide dismutase enzyme. However, in pathological situations, such as arterial hypertension, there may be an increase in the production of these radicals or a deficiency of the superoxide dismutase enzyme. In hypertensive patients, the release of vasoconstrictor peroxides derived from the activity of cyclo-oxygenase in the endothelium and the vascular smooth muscle is also important. The excess free radicals released by the dysfunctional endothelium also stimulate the synthesis of these contracting agents. Moreover, it should not be forgotten that endothelin-1, which is similarly synthesized and released in the vascular endothelium, is the most powerful known endogenous vasoconstrictor. This peptide would therefore play a prominent part in some forms of hypertension. Although no changes in endothelin plasma levels have been found in essential hypertension, there may be an increase in its local concentration. It should be borne in mind that endothelin could strengthen the effect of other vasoconstrictors. Moreover, it may also provoke the release of free radicals and of cyclo-oxygenase-derived vasoconstrictor factors. The latest theories therefore indicate that the increase in vasoconstriction, which characterizes arterial hypertension, is associated with a greater production of free radicals. At the present time, antioxidant agents and xanthine oxydase-inhibiting compounds are being used to treat hypertension and other pathologies linked to endothelial dysfunction. In addition, it is thought that the therapeutic benefit of some anti-hypertensive drugs, such as calcium antagonists and angiotensin-converting enzyme inhibitors, could be in part due to the inhibition of the production of free radicals that they provoke.

Involvement of the nitric oxide (NO) system in complications following human orthotopic liver transplants (OLT) has been reported, but the contribution of the graft to the modulation of the NO system during reperfusion in normal OLT has not been characterized. We have studied the contribution of the graft efflux to the modulation of the NO system in 20 consecutive OLT. We evaluated its effects on isolated vascular reactivity of the rabbit and on rat cultured macrophages stimulated with lipopolysaccharide (LPS). In none of the donor liver biopsies was expression of inducible NO synthase (iNOS) activity by Northern or Western blot analysis found. Graft efflux after the onset of liver reperfusion, but not pre-transplant patient plasma, reversibly inhibited the acetylcholine-induced relaxation of norepinephrine-contracted rabbit aortic rings. Moreover, graft efflux reversibly inhibited NO production in rat macrophages treated with LPS, as evidenced by both a decrease in nitrite plus nitrate formation and a decrease in the production of [ 14 C]citrulline from [ 14 C]arginine. Addition of a 10% dilution of graft efflux to cultured rat macrophages incubated with LPS increased iNOS mRNA levels, suggesting direct inhibition of the enzyme but not of its expression. These results cannot be ascribed to the depletion of arginine - the iNOS substrate - since they can be reproduced even in the presence of an excess.(10 mM) of exogenously added arginine. No correlation was found between the iNOS inhibitory activity in each sample and the corresponding clinical parameters related to either the graft function after the OLT or the existence of post-reperfusion syndrome. Our results indicate the existence of a soluble factor in the graft efflux from human OLT that reversibly and unspecifically inhibits NOS activity. Its involvement in the physiology and/or pathology of human liver diseases deserves further study.

Hypertension caused by calcium deficiency in the diet has been linked with an increase in parathyroid hormone (PTH) and calcitriol levels. We evaluated arterial blood pressure (ABP), PTH, and calcitriol in normotensive Sprague-Dawley rats (SDR) and in spontaneously hypertensive rats (SHR) fed from weaning on a control diet with a normal calcium content (1%) or a low-calcium diet (0.1%). The calcemia was also measured in the rats by colorimetric methods. The low-calcium diet decreased the calcemia in both strains and brought about an increase in the ABP which was significant in adult SDR and particularly noticeable during the early hypertensive phase in SHR. The rats fed on this diet had higher hormonal plasma levels when compared with the corresponding values in rats fed on the control diet. In particular, the SDR fed on the low-calcium diet showed much higher PTH (122.6 ± 31.0 pg/ml, p ≤ 0.05) and calcitriol (458.0 ± 13.1 pg/ml, p ≤ 0.01) values than the SDR fed on the control diet (PTH 31.7 ± 2.80 pg/ml; calcitriol 292.1 ± 17.5 pg/ml). These endocrine alterations could justify the increase in ABP caused by dietary calcium deficiency in normotensive rats. Nevertheless, the results of this study indicate that the modifications of the ABP caused by the low-calcium diet in SHR could not be correlated with significant increases in these hormones.

The endothelins (ET) are a family of contractile peptides made up of 21 amino acids. They are synthesised from larger precursors and they are expressed in different tissues. ET-1 is synthesised in endothelial cells by means of a specific endothelin converting enzyme and it is assumed that most of it is secreted into the basolateral compartment. It acts in a paracrine manner on the ETA and ETB2 receptors located on the surface of the vascular smooth muscle to elicit an increase in intracellular calcium and vasoconstriction. The circulating ET-1 can also activate endothelial ETC and ETB1 receptors releasing vascular smooth muscle relaxing factors, such as nitric oxide and prostacyclin. At present, it is generally accepted that ET-1 is a vasodilator in physiological conditions acting on endothelium ETB1 receptors. Nevertheless, in pathological situations such as hypertension, heart failure, acute myocardial infarction, acute renal failure and vasospastic conditions (Raynaud's disease and subarachnoid haemorrhage), ET-1 levels increase and it binds to the receptors present in vascular smooth muscle in such a way that its vasoconstrictor effect is manifested. Currently, experimental and clinical evidence exists to support the importance of the development of drugs that block the production or actions of ET for use in cardiovascular medicine, particularly in conditions in which these peptides are clearly implicated.

1. 1. Increase of Ca 2+ concentration in the bath solution diminishes the contractile response of isolated rabbit aorta rings to α 1 -adrenoceptor agonists and KCI. 2. 2. In intact preparations the contractions of methoxamine and phenylephrine were maximal when a 0.3- to 0.6-mM Ca 2+ bath solution was used, and those of KCI were maximal with a 2.5-mM Ca 2+ concentration. 3. 3. The contractions of methoxamine and phenylephrine also were decreased by increasing the Ca 2+ concentration above 1.25 mM in disrupted endothelium preparations and in those incubated in indomethacin (10 −5 M), N ω -nitro-L-arginine methyl ester (10 −4 M), or methylene blue (10 −6 M). 4. 4. High organ bath Ca 2+ concentrations also caused a decrease in KCI contractions using endotheliumdenuded and the treated preparations, the responses being similar with 1.25 mM and 2.5-mM Ca 2+ in the methylene blue-treated preparations, whereas they were greater with 1.25 mM Ca 2+ in the others.

In recent years, numerous studies have demonstrated the health benefits of polyphenols, and special attention has been paid to their beneficial effects against cardiovascular disease, the leading cause of death in the world today. Polyphenols present vasodilator effects and are able to improve lipid profiles and attenuate the oxidation of low density lipoproteins. In addition, they present clear anti-inflammatory effects and can modulate apoptotic processes in the vascular endothelium. It has been suggested that most of these effects are a consequence of the antioxidant properties of polyphenols, but this idea is not completely accepted, and many other mechanisms have been proposed recently to explain the health effects of these compounds. In fact, different signaling pathways have been linked to polyphenols. This review brings together some recent studies which establish the beneficial properties of polyphenols for cardiovascular disease and analyzes the mechanisms involved in these properties. © 2012 Elsevier Ltd., M. Miguel is the recipient of a Ramón y Cajal grant from Ministerio de Ciencia e Innovación. This work was supported by the Project Consolider Ingenio 2010 (CSD-2007-00063).

The consumption of dietary fiber (DF) has increased since it was related to the prevention of a range of illnesses and pathological conditions. DF can modify some gut hormones that regulate satiety and energy intake, thus also affecting lipid metabolism and energy expenditure. Among these gut hormones are ghrelin, glucagon-like peptide 1, peptide YY, and cholecystokinin. Adipose tissue is known to express and secrete a variety of products known as >adipocytokines,> which are also affected by DF. Some of the most relevant adipocytokines include adiponectin, leptin, tumor necrosis factor-α, and interleukin-6. The release of adipocytokines, by either adipocytes or macrophage-infiltrated adipose tissue, leads to a chronic subinflammatory state that could play a central role in the development of insulin resistance and type 2 diabetes, therefore increasing the risk of cardiovascular disease associated with obesity. DF modulation of these molecules could also have positive effects on obesity, insulin resistance, and hyperlipidemia. This review is focused on the effects of DF on the above-mentioned gut peptides and adipocytokines. © Copyright 2012, Mary Ann Liebert, Inc. and Korean Society of Food Science and Nutrition 2012., This study was supported by the Projects Consolider Ingenio 2010 (CSD-2007-00063) and AGL2008-01740. M.M. is the recipient of a Ramón y Cajal grant from the Ministerio de Ciencia e Innovación.

The involvement of endothelial-relaxing factors on the antihypertensive effect of a polyphenol-rich cocoa powder named CocoanOX (CCX) was studied. Thirty 17-20-week-old male spontaneously hypertensive rats (SHR), weighing 314 ± 3 g were used. They were divided into two groups of 15 animals, that were respectively administered by gastric intubation distilled water or 300 mg/kg CCX dissolved in distilled water, between 9 am and 10 am. 2 h after the oral administration, 5 of the animals in each group were intraperitoneally administered 1 ml saline. The remaining rats in both groups were divided into another two groups of 5 animals that were respectively administered 30 mg/kg Nw-nitro-l-arginine methyl ester (l-NAME) dissolved in 1 ml of saline or 5 mg/kg indomethacin also dissolved in 1 ml of saline by the same procedure. Systolic blood pressure (SBP) was recorded in the rats by the tail cuff method before the initial oral administration and also 4 h after this administration. CCX caused a significant decrease in SBP (-49.5 ± 4.9 mm Hg; p < 0.05). l-NAME caused a clear increase in SBP in the rats (+16.2 ± 4.3 mm Hg; p < 0.05), and the effect of CCX was not observed in the SHR that were treated with l-NAME (+4.1 ± 1.7 mm Hg; p < 0.05). Nevertheless, indomethacin treatment did not modify SBP in the SHR and this compound failed to modify the antihypertensive effect of CCX in these animals. In conclusion, this study proves the participation of NO in the antihypertensive effect of CCX in the SHR strain. When CCX is administered, the synthesis, or the bioavailability, of this endothelial factor could increase, but other mechanisms may also participate in the antihypertensive effect of this cocoa powder. In any case, further investigation should be carried out to characterize the signalling pathways involved in the antihypertensive effect of CCX. © 2011 Elsevier Ltd., This study was supported by Natraceutical Group (36/2007 U.C.M. Project).

In this study we evaluated the effect of the administration of different soluble fiber enriched-diets on inflammatory and redox state of Zucker fatty rats. Four groups of ten 8 week-old female Zucker fatty rats were used. The four groups were respectively fed the following diets until the 15th week of life: standard diet (obese control), 10% high methoxylated apple pectin (HMAP)-, 5% soluble cocoa fiber (SCF)-, and 10% β-glucan-enriched diets. A group of Zucker lean rats fed the standard diet was also used as control for normal values of this rat strain. The plasma levels of tumoral necrosis factor-α (TNF-α), adiponectin, and malondialdehyde (MDA) were measured at the end of treatment. The reduced glutathione liver levels were also obtained at that moment. TNF-α plasma levels decreased somewhat in Zucker fatty rats fed the different fibers, and MDA plasma levels significantly decreased in these animals. Nevertheless, adiponectin plasma levels increased in the Zucker fatty rats fed the SCF enriched diet, but did not change in the HMAP and the β-glucan group. The Zucker fatty rats fed the different fiber showed a trend towards increased the reduced glutathione liver levels, but significant differences with obese control rats were only obtained in the β-glucan group. The results obtained in this study suggest that the intake of the different soluble fiber-enriched diets that we have evaluated could prevent and/or attenuate the inflammatory and/or the prooxidative state of the metabolic syndrome. © 2011 Elsevier Ltd. All rights reserved.

In this study, we evaluated the short-term effect of a cocoa polyphenol extract (CPE), in spontaneously hypertensive rats (SHR). Male 17–22-week-old SHR were administered by intragastric gavage water, 50 mg kg−1 Captopril or CPE at different doses (13, 26, 80 and 160 mg kg−1). The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded by the tail cuff method before the administration and also 2, 4, 6, 8, 24, 48 and 72 h post-administration. Highly significant decreases in the SBP and in the DBP were observed when captopril or CPE was administered to SHR. The cocoa extract produced a dose dependent effect in the SBP of the SHR up to the dose of 80 mg kg−1. Nevertheless this dose of CPE did not decrease the arterial blood pressure in the normotensive Wistar Kyoto rats. The decrease in the SBP caused by 80 mg kg−1 of CPE in the SHR (−39.1 ± 3.7 mm Hg) was maximum 6 h post-administration, and the initial values of SBP were recovered 72 h post-administration of this extract. Paradoxically, 160 mg kg−1 of the cocoa extract caused a decreased antihypertensive effect than lower doses of CPE. In addition, the decrease in DBP was always more accentuated when the dose of CPE administered was lower. Our results suggest that CPE may be used as a functional food ingredient with beneficial effects for controlling arterial blood pressure., This study was supported by Natraceutical Group (36/2007 U.C. M. Project). Miguel M. holds a Ramon and Cajal work contract.

We investigate the mechanisms involved in the long-term antihypertensive effect of a polyphenol-rich cocoa powder, named CocoanOX® (CCX), in spontaneously hypertensive rats (SHR). We have carried out two different batches of experiments. For the first batch of experiments, forty 3 week-old male SHR were randomly divided with ad libitum intake into four groups of 10 animals, that respectively received the following drinking fluids up to the 20th week of life (treatment period): tap water (control), CCX 100 mg/kg/day, CCX 200 mg/kg/day and CCX 400 mg/kg/day. Five 20 week-old rats of each group were sacrificed by decapitation. From the 20th to 24th week of life all the remaining animals were given tap water (follow-up period), and all of them were sacrificed at the end of the follow-up period. Plasma malondialdehyde (MDA), reduced glutathione in the liver, plasma and aorta angiotensin converting enzyme (ACE) activity and plasma angiotensin II were determined in all the sacrificed SHR that were included in this batch of experiments. Plasma MDA decreased and liver reduced glutathione increased in the 20 week-old CCX treated SHR. These effects were not observed in the rats that were sacrificed after the follow-up period. CCX treatment did not modify aorta ACE activity, but the activity of ACE and the levels of angiotensin II increased in the plasma of the SHR treated with the highest dose of CCX. ACE activity returned to basal values in the SHR that were sacrificed after the follow-up period. However, angiotensin II levels were slightly higher after withdrawal of CCX.For the second batch of experiments we used aorta rings obtained from untreated SHR, and we evaluated the relaxation caused by CCX in different aorta preparations. CCX relaxed the intact aorta preparations but this cocoa did not relax the endothelium-denuded aorta rings from the untreated SHR. l-NAME, but not indomethacin, inhibited the relaxation caused by CCX in the SHR aorta rings. We postulate that the antihypertensive effect of CCX might be mediated by an improvement of endothelial release of nitric oxide and by a reduction of oxidative stress. The inhibition of ACE could be implicated in the antihypertensive effect of CCX. © 2010 Elsevier Ltd.

6 páginas, 3 figuras, 1 tabla., In this study we evaluated the short-term oral antihypertensive effect of several peptide sequences isolated from casein fractions, previously characterized as in vitro angiotensin-converting enzyme-inhibitors, in spontaneously hypertensive rats (SHR). Systolic blood pressure (SBP) and the diastolic blood pressure (DBP) of the rats were measured by the tail cuff method before administration and also 2, 4, 6, 8 and 24 h post-administration. The sequences LVYPFTGPIPN, HLPLP, IAK, YAKPVA and WQVLPNAVPAK showed a clear decrease in SBP and DBP in SHR. HPHPHLSF caused a significant decrease of the DBP in the SHR, but this sequence did not modify the SBP of these animals in a significant manner. KKYNVPQL did not modify SBP in the SHR, and caused a slight, but significant and maintained, decrease in DBP in these animals. SBP and DBP returned to baseline values 24 h post-administration of all peptides. In conclusion, these peptides are bioactive ingredients with potential benefit in the prevention and treatment of hypertension or other associated disorders., This study has received financial support from the projects AGL2007-65035, AGL2008-01713 and CSD-2007-00063. Marta Miguel is the recipient of a Ramón y Cajal contract from MICINN.

9 páginas, 8 figuras, 2 tablas., The effect produced by long-term intake of a soluble cocoa fiber product (SCFP) on the development of hypertension of spontaneously hypertensive rats (SHR) was evaluated. Twenty male 3-week-old SHR were divided into two groups of 10 animals that drank either tap water (control) or a solution of SCFP (0.75 g/day SCFP) until the 20th week of life. Five 20-week-old rats of each group were sacrificed. Tap water as drinking fluid was given to all the animals from the 20th to 24th week of life. The 24-week-old rats were also sacrificed. Body weight, liquid and dry food intake, and arterial blood pressure (tail cuff) were recorded weekly. Malondialdehyde (MDA), glucose and angiotensin converting enzyme (ACE) activity in the plasma from the sacrificed rats were also obtained, and we evaluated the relaxation caused by acetylcholine in the aorta from these animals. SCFP attenuated the development of hypertension in SHR; however, the withdrawal of SCFP caused an increase in blood pressure in the rats. Body weight gain was slower in the group treated with SCFP. SCFP increased liquid intake but decreased dry food intake in the rats. SCFP decreased plasma MDA concentrations and slightly decreased plasma ACE activity, but no differences were observed in plasma glucose and in the aorta responses to acetylcholine in both groups of 20-week-old SHR. We have demonstrated the antihypertensive and antioxidant properties of SCFP. The control of body weight and the control of increased angiotensin II may be involved in the antihypertensive effect of this product., This study was supported by Natraceutical Group (36/2007 UCM Project).

We have evaluated the effect of the long-term intake of a cocoa powder, with high concentration of polyphenols, named CocoanOX (CCX), on the development of hypertension of spontaneously hypertensive rats (SHR). Systolic blood pressure was measured weekly in the rats, from the 6th to 24th week of life, by the tail cuff method. The development of hypertension was attenuated in the groups treated with captopril or CCX. The antihypertensive effect was more accentuated in the group treated with captopril, and it was paradoxically more accentuated in the group treated with the lowest dose of CCX than in the other CCX groups. The arterial blood pressure increased in the treated SHR when the corresponding antihypertensive treatment was removed. Both, CCX and the standard cocoa, improved the aorta endothelial function in the SHR. In conclusion, CCX could be used as a functional food ingredient with antihypertensive activity. © 2010 Elsevier Ltd. All rights reserved.

A natural flavonoid-enriched cocoa powder, commercially named CocoanOX and developed via a patented industrial process, was characterized and tested for a possible antihypertensive effect. The bioavailability of this polyphenol-rich cocoa powder developed at pilot scale was previously demonstrated in humans. The present results showed that this product was very rich in total procyanidins (128.9 mg/g), especially monomers, dimers, and trimers (54.1 mg/g), and mainly (-)-epicatechin (19.36 mg/g). The effect of a single oral administration of CocoanOX in spontaneously hypertensive rats (SHR) was evaluated at different doses (50, 100, 300, and 600 mg/kg). This product produced a clear antihypertensive effect in these animals, but these doses did not modify the arterial blood pressure in the normotensive Wistar-Kyoto rats. Paradoxically, the maximum effect in the systolic blood pressure (SBP) of SHR was caused by 300 mg/kg of CocoanOX. This dose brought about a decrease in this variable very similar to that caused by 50 mg/kg Captopril. It was also surprising that the maximum effect in the diastolic blood pressure (DBP) was caused by 100 mg/kg CocoanOX. The initial values of DBP and SBP were recovered in SHR, respectively, 24 and 48 h postadministration of the different doses of CocoanOX or Captopril. These results suggest that CocoanOX could be used as a functional ingredient with antihypertensive effect, although it would be also necessary to carry out bioavailability and clinical studies to demonstrate its long-term antihypertensive efficiency in humans.

Inclusion of fiber in the diet has been linked to the prevention of a range of illnesses and conditions. This review contains several ideas about the possible benefits of dietary fiber intake in patients with metabolic syndrome. The principal beneficial effects of a fiber-rich diet in these patients are: prevention of obesity, improved glucose levels, and control of the profile of blood lipids. We now also know that dietary fiber may favor the control of arterial blood pressure. Animal experiments have also shown the benefit of different types of fiber on these variables. Of particular relevance are the studies using obese Zucker rats, which present similar anomalies to those seen in patients with metabolic syndrome. There is therefore a growing interest in discovering new sources of natural fiber. Some of these different kinds of fiber may then be used as functional ingredients to obtain foods with properties that are beneficial to health.

In this study, we have identified novel antihypertensive peptides derived from egg-white proteins. The sequences YRGGLEPINF and ESIINF produced an acute blood-pressure-lowering effect in spontaneously hypertensive rats upon a single oral administration. Our results suggest that the antihypertensive action could be attributed to a vascular-relaxing mechanism that would occur in vivo independently of angiotensin I-converting enzyme (ACE) inhibition, because neither these peptides nor their main digestion fragments, except for the dipeptide YR, acted as ACE inhibitors in vitro. The vasodilator and antihypertensive activity of the sequences ESI and NF would explain the blood-pressure-lowering effect of ESIINF. With regard to YRGGLEPINF, in addition to NF, YR appeared as the main fragment responsible for its activity. The dipeptide YR, named kyotorphin and previously identified as an endogenous analgesic neuropeptide in the central nervous system, showed strong vasodilator and antihypertensive properties. The structure-activity features of the vasodilator peptides are discussed.

Zucker fatty rats are the best known animal model of genetic obesity. Obesity in these animals is inherited as an autosomal recessive trait. Affected rats have a mutation in the leptin receptor and show hyperphagia and other alterations similar to those that appear in human metabolic syndrome. These animals have hyperinsulinemia and can also be considered a model of insulin resistance. Nevertheless, the usefulness of Zucker fatty rats as a model of type 2 diabetes is questionable, since these animals have only mild glucose intolerance. The lipid profile in these animals is also altered. These rats show an increase in both very low density lipoproteins (VLDL) and high density lipoproteins (HDL) but no increase in LDL cholesterol and these animals cannot be used as a model for atherogenesis. Zucker obese rats are not a model for hypertension either, even though they show high systolic blood pressure values after 28 weeks of life.

In this study, the antihypertensive activity in spontaneously hypertensive rats of two peptides isolated from β-lactoglobulin hydrolysates with thermolysin was evaluated. These peptides, with sequences LLF [β-lg f(103–105)] and LQKW [β-lg f(58–61)], showed potent in vitro ACE-inhibitory activity. Two hours after administration, both sequences caused a clear and significant decrease in the blood pressure of these rats. The impact of a simulated gastrointestinal digestion on ACE-inhibitory and antihypertensive activities of these peptides was also studied. The results showed that both fragments were susceptible to proteolytic degradation after incubation with pepsin and Corolase PP®. In addition, their in vitro ACE-inhibitory activity decreased after the simulated digestion. It is likely that fragment LQK was the active end product of the gastrointestinal digestion of peptide LQKW. The fragment LL, observed after digestion of peptide LLF, probably exert its antihypertensive effect through a mechanism of action different than ACE-inhibition.

9 páginas, 4 figuras, 3 tablas.-- PMID: 17106083 [PubMed]., El artículo se puede acceder gratuitamente a través de la web del editor, Among different lactic acid bacteria isolated from raw milk, 4 Enterococcus faecalis strains have stood out as producers of fermented milk with potent antihyperten-sive activity. The peptide ß-casein f(133–138), LHLPLP, was identified as one of the major peptides responsible for the activity of these fermented milk products. A simple method was developed to quantify this peptide in fermented milk using high-performance liquid chromatography coupled in line with mass spectrometry. This procedure does not require any previous sample fractionation or extraction, and direct analysis of the water-soluble extract obtained from the fermented milk can be performed. Validation studies showed sufficient speci-ficity, reproducibility, linearity, and recovery, demonstrating that this method can be used for the routine quantification of LHLPLP during the production of fermented milk products. The developed method was readily applied to quantify the peptide LHLPLP under different fermentation conditions and with different aromatized products., This work has received financial support from the projects AGL2004-06903-C02-01 from the Ministerio de Educación y Ciencia, and CM-S0505-AGR-0153 financed by Comunidad de Madrid. A. Quirós was the recipient of a fellowship from the I3P Programme from the Consejo Superior de Investigaciones Científicas.

A total of 231 microorganisms were isolated from raw cow milk samples and the angiotensin-converting enzyme-inhibitory (ACEI) activity of the resultant fermented milk produced with the isolated microorganisms was assayed. Forty-six of these microorganisms were selected on the basis of high ACEI activity. Four Enterococcus faecalis strains stood out as producers of fermented milk with potent ACEI activity (IC50 (the protein concentration that inhibits 50% of ACE activity): 34–59 μg mL−1). Single doses (5 mL kg−1) of the whey fraction obtained from these fermented milk samples were administered to spontaneously hypertensive rats (SHR) and to normotensive Wistar-Kyoto (WKY) rats in order to investigate their possible antihypertensive activity. Highly significant decreases in the systolic blood pressure (SBP) and in the diastolic blood pressure (DBP) were observed when the fermented milk was administered to SHR. Nevertheless, the fermented milk did not modify the SBP and the DBP of the WKY rats. Raw cow milk is an excellent source of wild lactic acid bacteria able to produce fermented milk with antihypertensive activity and antihypertensive activity of milk fermented by Enterococcus faecalis strains was associated with peptides different from Ile-Pro-Pro and Val-Pro-Pro.

This paper evaluates the effect of the long-term intake of a hydrolysate of egg white with pepsin (HEW), with a potent angiotensin converting enzyme inhibitory activity, on the development of hypertension of spontaneously hypertensive rats (SHR). After being weaned, male 3-week-old SHR were randomly divided into five groups that were given until the 20th week of life the following drinking fluids: (1) tap water, (2) non-treated egg white 1 g/kg/day, (3) captopril 100 mg/kg/day, (4) HEW 0.5 g/kg/day, and (5) HEW 1 g/kg/day. From the 20th to 25th week of life, animals from all groups were given tap water. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured weekly in the rats, from the 6th to 25th week of life, by the tail cuff method. Development of hypertension was attenuated in the groups treated with captopril and HEW (P < 0.001 vs. the group that drunk tap water). At the 20th week of life, the arterial blood pressure values of the different groups of rats were: tap water (SBP = 219.5 ± 5.7, DBP = 167 ± 3.7), non-treated egg white (SBP = 206.4 ± 1.43, DBP = 166.4 ± 4.9), captopril (SBP = 131.7 ± 2.74, DBP = 91.5 ± 1.62), HEW 0.5 g/kg/day (SBP = 182.9 ± 4.64, DBP = 127.5 ± 2.1) and HEW 1 g/kg/day (SBP = 177.7 ± 4.72, DBP = 120.1 ± 2.4). SBP and DBP increased in the treated SHR when the corresponding antihypertensive treatment was removed. In spite of this, SBP remained lower in the SHR that had received captopril and HEW than in the SHR of the control groups (P < 0.05). The present results suggest that HEW could be used as a functional food with antihypertensive activity. © 2005 Elsevier Inc. All rights reserved., This study was supported by the project (AGL2004-06903-C02-00).

In the present study we evaluate the blood pressure-lowering effect of the following products: the hydrolysate obtained from egg white (EW) by enzymatic treatment with pepsin (HEW), the peptide fraction of HEW with molecular mass lower than 3000 Da (HEW, This study was supported by an INIA-MCYT project (CAL01-046-02) and an MCYT project (AGL2000-1480)

It has been shown that calcium-enriched diets cause a decrease in arterial blood pressure in hypertensive patients and animals. Moreover, it has been suggested that the combination of dietary calcium and calcium antagonists could paradoxically have a synergistic effect in order to decrease arterial blood pressure. The combination of these treatments may also have potential therapeutic benefit in the attenuation of cardiac hypertrophy. In this study, after being weaned at three weeks, male spontaneously hypertensive rats (SHR) were randomized in four groups of animals. Two of these groups were fed on a normal calcium diet (Ca 1%) and another two groups were fed on a calcium-enriched diet (Ca 2.5%). One of the groups fed on each diet also received amlodipine (1 mg/kg/day) in the drinking water after being weaned. Body weight was measured weekly in all the groups, and arterial blood pressure was also measured in all the 10-, 15-, 20-, and 25-week-old SHR by the tail cuff method. We established the ratio heart weight/body weight x 1000 (R), and we weighed the left ventricle in the 25-week-old animals at the end of the different treatments. The Ca 2.5% diet caused a delay in the development of hypertension in SHR. This effect could not be correlated with alterations in body weight since this diet improved growth in these rats. Amlodipine did not alter growth in SHR. This pharmacological treatment caused a decrease in the arterial blood pressure of the SHR and it intensified the antihypertensive effect of the Ca 2.5% diet. Nevertheless, this drug attenuated the effect of dietary calcium on body weight and when the treatment was prolonged, almodipine also antagonized the effect of dietary calcium on arterial blood pressure. At the end of the different treatments the ratio R and the left ventricular weight were similar in all the groups of animals. Therefore, the use of dietary calcium with a calcium antagonist to control arterial blood pressure seems not to be advisable, and the present data do not prove the usefulness of the mentioned antihypertensive treatments in preventing cardiac hypertrophy.