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Objective To investigate the relationship of miRNA gene polymorphisms with blood pressure (BP) responses to the sodium and potassium diet intervention. Methods In 2004, we recruited 514 participants from 124 families in seven villages of Baoji, Shaanxi Province, China. All subjects were given a three-day normal diet, followed by a seven-day low-salt diet, a seven-day high-salt diet, and finally a seven-day high-salt and potassium supplementation. A total of 19 miRNA single nucleotide polymorphisms (SNPs) were selected for analysis. Results Throughout the sodium-potassium dietary intervention, the BP of the subjects fluctuated across all phases, showing a decrease during the low-salt period and an increase during the high-salt period, followed by a reduction in BP subsequent to potassium supplementation during the high-salt diet. MiR-210-3p SNP rs12364149 was significantly associated with systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure (MAP) responses to low-salt diet. MiR-4638-3p SNP rs6601178 was significantly associated with SBP while miR-26b-3p SNP rs115254818 was significantly associated with MAP responses to low-salt intervention. In addition, miR-26b-3p SNP rs115254818 was significantly correlated with SBP, DBP and MAP responses to high-salt intervention. MiR-1307-5p SNPs rs11191676 and rs2292807 were associated with SBP and MAP responses to high-salt diet. MiR-4638-3p SNP rs6601178, miR- 210-3p SNP rs12364149, miR-382-5p SNP rs4906032 and rs4143957 were significantly associated with SBP response to high-salt diet. In addition, miR-26b-3p SNP rs115254818 was significantly associated with SBP, DBP and MAP responses to potassium supplementation. MiR-1307-5p SNPs rs11191676, rs2292807, and miR-19a-3p SNP rs4284505 were significantly associated with SBP responses to high-salt and potassium supplementation. Conclusion miRNA gene polymorphisms are associated with BP response to sodium and potassium, suggesting that miRNA genes may be involved in the pathophysiological process of salt sensitivity and potassium sensitivity. [ABSTRACT FROM AUTHOR]

Previous transplantation studies and the concept of 'nephron underdosing' support the idea that the kidney plays a crucial role in the development of essential hypertension. This suggests that there are genetic factors in the kidney that can either elevate or decrease blood pressure. The kidney normally maintains arterial pressure within a narrow range by employing the mechanism of pressure-natriuresis. Hypertension is induced when the pressure-natriuresis mechanism fails due to both subtle and overt kidney abnormalities. The inheritance of hypertension is believed to be polygenic, and essential hypertension may result from a combination of genetic variants that code for renal tubular sodium transporters or proteins involved in regulatory pathways. The renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS) are the major regulators of renal sodium reabsorption. Hyperactivity of either the RAAS or SNS leads to a rightward shift in the pressure-natriuresis curve. In other words, hypertension is induced when the activity of RAAS and SNS is not suppressed despite increased salt intake. Sodium overload, caused by increased intake and/or reduced renal excretion, not only leads to an expansion of plasma volume but also to an increase in systemic vascular resistance. Endothelial dysfunction is caused by an increased intracellular Na+ concentration, which inhibits endothelial nitric oxide (NO) synthase and reduces NO production. The stiffness of vascular smooth muscle cells is increased by the accumulation of intracellular Na+ and subsequent elevation of cytoplasmic Ca++ concentration. In contrast to the hemodynamic effects of osmotically active Na+, osmotically inactive Na+ stimulates immune cells and produces proinflammatory cytokines, which contribute to hypertension. When this occurs in the gut, the microbiota may become imbalanced, leading to intestinal inflammation and systemic hypertension. In conclusion, the primary cause of hypertension is sodium overload resulting from kidney dysregulation. [ABSTRACT FROM AUTHOR]

Recent studies, conducted mainly on the rodent model, have demonstrated that regulatory pathway in the skin provided by glycosaminoglycans, nuclear factor of activated T cells 5 (NFAT5), vascular endothelial growth factor C (VEGF-C) and process of lymphangiogenesis may play an important role in extrarenal regulation of sodium (Na+) balance, body water volume, and blood pressure. We aimed to investigate the concentrations and relations among the main factors of this pathway in human skin to confirm that this regulatory axis also exists in humans. Skin specimens from patients diagnosed with arterial hypertension and from control group were histologically and molecularly examined. The primary hypertensive and control groups did not differ in Na+ ​concentrations in the skin. However, the patients with hypertension and higher skin Na+ concentration had significantly greater density of skin lymphatic vessels. Higher skin Na+concentration was associated with higher skin water content. In turn, skin water content correlated with factors associated with lymphangiogenesis , i.e. NFAT5, VEGF-C, and podoplanin (PDPN) mRNA expression in the skin. The strong mutual pairwise correlations of the expressions of NFAT5, VEGF-C, vascular endothelial growth factor D (VEGF-D) and PDPN mRNA were noted in the skin in all of the studied groups. Our study confirms that skin interstitium and the lymphatic system may be important players in the pathophysiology of arterial hypertension in humans. Based on the results of our study and existing literature in this field, we propose the hypothetical model which might explain the phenomenon of salt-sensitivity. [ABSTRACT FROM AUTHOR]

Previous transplantation studies and the concept of ‘nephron underdosing’ support the idea that the kidney plays a crucial role in the development of essential hypertension. This suggests that there are genetic factors in the kidney that can either elevate or decrease blood pressure. The kidney normally maintains arterial pressure within a narrow range by employing the mechanism of pressure-natriuresis. Hypertension is induced when the pressure-natriuresis mechanism fails due to both subtle and overt kidney abnormalities. The inheritance of hypertension is believed to be polygenic, and essential hypertension may result from a combination of genetic variants that code for renal tubular sodium transporters or proteins involved in regulatory pathways. The renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS) are the major regulators of renal sodium reabsorption. Hyperactivity of either the RAAS or SNS leads to a rightward shift in the pressure-natriuresis curve. In other words, hypertension is induced when the activity of RAAS and SNS is not suppressed despite increased salt intake. Sodium overload, caused by increased intake and/or reduced renal excretion, not only leads to an expansion of plasma volume but also to an increase in systemic vascular resistance. Endothelial dysfunction is caused by an increased intracellular Na+ concentration, which inhibits endothelial nitric oxide (NO) synthase and reduces NO production. The stiffness of vascular smooth muscle cells is increased by the accumulation of intracellular Na+ and subsequent elevation of cytoplasmic Ca++ concentration. In contrast to the hemodynamic effects of osmotically active Na+, osmotically inactive Na+ stimulates immune cells and produces proinflammatory cytokines, which contribute to hypertension. When this occurs in the gut, the microbiota may become imbalanced, leading to intestinal inflammation and systemic hypertension. In conclusion, the primary cause of hypertension is sodium overload resulting from kidney dysregulation.

Spreading depolarization (SD) occurs in a plethora of clinical conditions including migraine aura, delayed ischemia after subarachnoid hemorrhage and malignant hemispheric stroke. It describes waves of near-breakdown of ion homeostasis, particularly Na+ homeostasis in brain gray matter. SD induces tone alterations in resistance vessels, causing either hyperperfusion in healthy tissue; or hypoperfusion (inverse hemodynamic response = spreading ischemia) in tissue at risk. Observations from mice with genetic dysfunction of the ATP1A2-encoded α2-isoform of Na+/K+-ATPase (α2NaKA) suggest a mechanistic link between (1) SD, (2) vascular dysfunction, and (3) salt-sensitive hypertension via α2NaKA. Thus, α2NaKA-dysfunctional mice are more susceptible to SD and show a shift toward more inverse hemodynamic responses. α2NaKA-dysfunctional patients suffer from familial hemiplegic migraine type 2, a Mendelian model disease of SD. α2NaKA-dysfunctional mice are also a genetic model of salt-sensitive hypertension. To determine whether SD thresholds and hemodynamic responses are also altered in other genetic models of salt-sensitive hypertension, we examined these variables in stroke-prone spontaneously hypertensive rats (SHRsp). Compared with Wistar Kyoto control rats, we found in SHRsp that electrical SD threshold was significantly reduced, propagation speed was increased, and inverse hemodynamic responses were prolonged. These results may have relevance to both migraine with aura and stroke. [ABSTRACT FROM AUTHOR]

Salt-sensitive (SS) hypertension is accompanied with severe cardiorenal complications. In this condition, elevated blood pressure (BP) resulting from salt retention is associated with counterintuitively lower levels of atrial natriuretic peptide (ANP). In plasma, ANP is degraded by the neprilysin; therefore, pharmacological inhibition of this metalloprotease (i.e., with sacubitril) can be employed to increase ANP level. We have shown earlier that sacubitril in combination with valsartan (75 μg/day each) had beneficial effects on renal function in Dahl SS rats. The goal of this study was to evaluate the effects of a higher dose of sacubitril on renal damage in this model. To induce hypertension, male Dahl SS rats were fed a 4% NaCl diet (HS) for 21 days, and were administered sacubitril (125 μg/day) or vehicle via s.c. osmotic pumps. At the end of the HS challenge, both groups exhibited similar outcomes for GFR, heart weight, plasma electrolytes, BUN, and creatinine. Sacubitril exacerbated kidney hypertrophy, but did not affect levels of renal fibrosis. We also observed aggravated glomerular lesions and increased formation of protein casts in the sacubitril-treated animals compared to controls. Thus, in Dahl SS rats, administration of sacubitril without renin-angiotensin-system blockage had adverse effects on renal disease progression, particularly in regards to glomerular damage and protein cast formation. We can speculate that while ANP levels are increased because of neprilysin inhibition, there are off-target effects of sacubitril, which are detrimental to renal function in the SS hypertensive state.

It is widely held that in response to high salt diets, normal individuals are acutely and chronically resistant to salt-induced hypertension because they rapidly excrete salt and retain little of it so that their blood volume, and therefore blood pressure, does not increase. Conversely, it is also widely held that salt-sensitive individuals develop salt-induced hypertension because of an impaired renal capacity to excrete salt that causes greater salt retention and blood volume expansion than that which occurs in normal salt-resistant individuals. Here we review results of both acute and chronic salt-loading studies that have compared salt-induced changes in sodium retention and blood volume between normal subjects (salt-resistant normotensive control subjects) and salt-sensitive subjects. The results of properly controlled studies strongly support an alternative view: during acute or chronic increases in salt intake, normal salt-resistant subjects undergo substantial salt retention and do not excrete salt more rapidly, retain less sodium, or undergo lesser blood volume expansion than do salt-sensitive subjects. These observations: (i) directly conflict with the widely held view that renal excretion of sodium accounts for resistance to salt-induced hypertension, and (ii) have implications for contemporary understanding of how various genetic, immunologic, and other factors determine acute and chronic blood pressure responses to high salt diets.

[Display omitted] The salinity at which the dynamic phase inversion of the reference system C 10 E 4 /n -Octane / Water occurs in the presence of increasing amounts of a test surfactant S 2 provides quantitative information on the hydrophilic/lipophilic ratio and on the sensitivity to NaCl aq of S 2. The Salinities causing the Phase Inversion (SPI) of the reference system mixed with 12 ionic and 10 nonionic well-defined surfactants are determined in order to quantify the contributions of the nature of the polar head and of the alkyl chain length. The SPI varies linearly upon the addition of S 2. The slope of the straight variation with the molar fraction of S 2 is called the "SPI-slope". It quantifies the hydrophilic/lipophilic ratio of S 2 in saline environment and its salt-sensitivity with respect to the reference surfactant C 10 E 4. The SPI-slopes of C 12 surfactants bearing different polar heads are found to decrease in the following order: C 12 NMe 3 Br > C 12 E 8 > C 12 E 7 ≥C 12 SO 3 Na ≈ C 12 COONa ≥ C 12 SO 4 Na > C 12 E 6 > C 12 E 5 > C 12 E 3. This classification is different from that obtained when the phase inversion is caused by a change in temperature (PIT-slope method) because the addition of NaCl in significant amounts (3 to 10 wt%) partially screens the ionic heads and diminishes their apparent hydrophilicities. A simple model, valid for all types of nonionic surfactants, is developed on the basis of the HLD N equation (Normalized Hydrophilic-Lipophilic Deviation) to express the SPI-slope as a function of the hydrophilic/lipophilic ratio (PACN 2) and the salinity coefficient (δ 2) of S 2. All studied surfactants are positioned on a 2D map according to the values of their SPI-slope and their PIT-slope to graphically highlight their hydrophilic/lipophilic ratio and their salt-sensitivity. Finally, a linear model connecting the PIT-slope and the SPI-slope is derived for nonionics, emphasizing that the thermal partitioning of C 10 E 4 towards n-octane is much greater in the PIT-slope than in the SPI-slope experiments. [ABSTRACT FROM AUTHOR]

Stimuli‐sensitive polymers are a class of macromolecular system with "intelligent" behavior. Herein, a copolymer of poly (acrylamide‐co‐2‐acrylamido‐dodecyl sulfonate), which has salt‐sensitive and thermosensitive properties, is synthesized via precipitation polymerization. Its aqueous solution exhibits a clear sol state, while a gel is obtained via salt‐induction by addition a certain amount of NaCl. More interestingly, the gel can transform into clear sol again upon heating, which exhibits a phase transition of upper critical solution temperature in NaCl solution. The dual responsive behaviors of copolymer solutions are studied via rheological measurements. Then fluorescence spectrum, zeta potential test, and dynamic light scattering are employed to investigate molecular interaction in aqueous solution under varying conditions. It is found that dual responsive behaviors are caused by electrostatic interaction and hydrophobic association. At last, oily emulsion wastewater treatment indicates that this polymer shows characteristics of "smart flocculant" and has potential application prospect. [ABSTRACT FROM AUTHOR]

Background. Effective drug therapy for resistant arterial hypertension is among major problems in modern medicine. The actual prevalence of resistant arterial hypertension is unknown, and its pathogenetic mechanisms are actively investigated. Among its important components is salt-sensitivity of the patient. At the same time, effi cacy of combined antihypertensive therapy in relation to salt-sensitivity of patients with resistant arterial hypertension is not fully understood.Objectives. Effi cacy assessment of personalised drug therapy in salt-sensitive and salt-resistant patients with resistant arterial hypertension.Мethods. We conducted a non-randomised controlled study with the observation time of 48 weeks. All patients had ambulatory blood pressure monitoring (ABPM) in the onset and past 48 weeks of treatment. Prior to therapy, the patient’s salt-sensitivity was determined with ABPM in salt loading (V.I. Kharchenko’s test). Two cohorts were formed with respect to the test results to include salt-sensitive (n = 67) and salt-resistant (n = 54) patients. Both cohorts received a combined therapy: enalapril 10 mg twice a day, amlodipine 10 mg/day, hydrochlorothiazide 12.5 mg/day, aliskiren 150 mg/day. If a target blood pressure was not observed in 3 weeks, aliskiren was elevated to 300 mg/day. Therapeutic effi cacy was assessed with ABPM after 48 weeks. Non-parametric statistical analysis was performed using Statistica 6.10 (StatSoftInc, USA).Results. The study included 121 patients with resistant arterial hypertension, median age 63 [58;67]. With background therapy, the target blood pressure was observed in 29 (43.4%) patients in cohort 1 and in 38 (70.4%) — in cohort 2 (intergroup p < 0.05). Statistically signifi cant lower ABPM values were registered in both cohorts after 48 weeks. Daily blood pressure normalised with therapy in 62.1% of patients in cohort 1 and in 68.4% — in cohort 2. The salt-resistant cohort exhibited a more pronounced reduction in ABPM values compared to salt-sensitive patients.Conclusion. Salt-sensitivity is a factor for personalising antihypertensive drug therapy in patients with resistant arterial hypertension due to specifi city of mechanisms for maintaining high blood pressure. Combined antihypertensive therapy with aliskiren is statistically more effective in salt-resistant than in salt-sensitive patients.

Salt sensitivity of blood pressure (SSBP) is an independent risk factor for cardiovascular morbidity and mortality that is seen in both hypertensive and normotensive populations. Insulin resistance (IR) strongly correlates with SSBP and affects nearly 50% of salt sensitive people. While the precise mechanism by which IR and SSBP relate remains elusive, several common pathways are involved in the genesis of both processes, including vascular dysfunction and immune activation. Vascular dysfunction associated with insulin resistance is characterized by loss of nitric oxide (NO)-mediated vasodilation and heightened endothelin-1 induced vasoconstriction, as well as capillary rarefaction. It manifests with increased blood pressure (BP) in salt sensitive murine models. Another common denominator in the pathogenesis of insulin resistance, hypertension, and salt sensitivity (SS) is immune activation involving pro-inflammatory cytokines like tumor necrosis factor (TNF)-α, IL-1β, and IL-6. In the last decade, a new understanding of interstitial sodium storage in tissues such as skin and muscle has revolutionized traditional concepts of body sodium handling and pathogenesis of SS. We have shown that interstitial Na+ can trigger a T cell mediated inflammatory response through formation of isolevuglandin protein adducts in antigen presenting cells (APCs), and that this response is implicated in salt sensitive hypertension. The peroxisome proliferator-activated receptor γ (PPARγ) is a transcription factor that modulates both insulin sensitivity and BP. PPARγ agonists increase insulin sensitivity and ameliorate salt sensitivity, whereas deficiency of PPARγ results in severe insulin resistance and hypertension. These findings suggest that PPARγ plays a role in the common pathogenesis of insulin sensitivity and salt sensitivity, perhaps via effects on the immune system and vascular function. The goal of this review is to discuss those mechanisms that may play a role in both SSBP and in insulin resistance. [ABSTRACT FROM AUTHOR]

Salt-sensitive (SS) hypertension is accompanied with severe cardiorenal complications. In this condition, elevated blood pressure (BP) resulting from salt retention is associated with counterintuitively lower levels of atrial natriuretic peptide (ANP). In plasma, ANP is degraded by the neprilysin; therefore, pharmacological inhibition of this metalloprotease (i.e., with sacubitril) can be employed to increase ANP level. We have shown earlier that sacubitril in combination with valsartan (75 μg/day each) had beneficial effects on renal function in Dahl SS rats. The goal of this study was to evaluate the effects of a higher dose of sacubitril on renal damage in this model. To induce hypertension, male Dahl SS rats were fed a 4% NaCl diet (HS) for 21 days, and were administered sacubitril (125 μg/day) or vehicle via s.c. osmotic pumps. At the end of the HS challenge, both groups exhibited similar outcomes for GFR, heart weight, plasma electrolytes, BUN, and creatinine. Sacubitril exacerbated kidney hypertrophy, but did not affect levels of renal fibrosis. We also observed aggravated glomerular lesions and increased formation of protein casts in the sacubitril-treated animals compared to controls. Thus, in Dahl SS rats, administration of sacubitril without renin-angiotensin-system blockage had adverse effects on renal disease progression, particularly in regards to glomerular damage and protein cast formation. We can speculate that while ANP levels are increased because of neprilysin inhibition, there are off-target effects of sacubitril, which are detrimental to renal function in the SS hypertensive state. [ABSTRACT FROM AUTHOR]

Salt sensitivity of blood pressure (SSBP) is an independent risk factor for cardiovascular morbidity and mortality that is seen in both hypertensive and normotensive populations. Insulin resistance (IR) strongly correlates with SSBP and affects nearly 50% of salt sensitive people. While the precise mechanism by which IR and SSBP relate remains elusive, several common pathways are involved in the genesis of both processes, including vascular dysfunction and immune activation. Vascular dysfunction associated with insulin resistance is characterized by loss of nitric oxide (NO)-mediated vasodilation and heightened endothelin-1 induced vasoconstriction, as well as capillary rarefaction. It manifests with increased blood pressure (BP) in salt sensitive murine models. Another common denominator in the pathogenesis of insulin resistance, hypertension, and salt sensitivity (SS) is immune activation involving pro-inflammatory cytokines like tumor necrosis factor (TNF)-α, IL-1β, and IL-6. In the last decade, a new understanding of interstitial sodium storage in tissues such as skin and muscle has revolutionized traditional concepts of body sodium handling and pathogenesis of SS. We have shown that interstitial Na+ can trigger a T cell mediated inflammatory response through formation of isolevuglandin protein adducts in antigen presenting cells (APCs), and that this response is implicated in salt sensitive hypertension. The peroxisome proliferator-activated receptor γ (PPARγ) is a transcription factor that modulates both insulin sensitivity and BP. PPARγ agonists increase insulin sensitivity and ameliorate salt sensitivity, whereas deficiency of PPARγ results in severe insulin resistance and hypertension. These findings suggest that PPARγ plays a role in the common pathogenesis of insulin sensitivity and salt sensitivity, perhaps via effects on the immune system and vascular function. The goal of this review is to discuss those mechanisms that may play a role in both SSBP and in insulin resistance.

Abstract Objective The objective of this study is to quantify and compare the effect of excess dietary salt on immune cell activation and blood pressure in HIV versus HIV negative individuals. Results Salt-sensitivity is associated with increased immune cell activation in animal studies. This concept has not been tested in people living with HIV. This study will therefore add more information in elucidating the interaction between HIV infection and/or anti-retroviral therapy (ART), immune-activation/inflammation and hypertension.

Background The regulation of sodium excretion is important in the pathogenesis of hypertension and salt sensitivity is predictive of cardiovascular events and mortality. C57Bl/6 and BALB/c mice have different blood pressure sensitivities to salt intake. High salt intake increases blood pressure in some C57Bl/6J mouse strains but not in any BALB/c mouse strain. Methods and Results We determined the cause of the difference in salt sensitivity between C57Bl/6 and BALB/c mice. Basal levels of superoxide and H2O2 were higher in renal proximal tubule cells (RPTCs) from BALB/c than C57Bl/6J mice. High salt diet increased H2O2 production in kidneys from BALB/c but C57Bl/6J mice. High sodium concentration (170 mmol/L) in the incubation medium increased H2O2 levels in BALB/c‐RPTCs but not in C57Bl/6J‐RPTCs. H2O2 (10 μmol/L) treatment decreased sodium transport in RPTCs from BALB/c but not C57Bl/6J mice. Overexpression of catalase in the mouse kidney predisposed BALB/c mice to salt‐sensitive hypertension. Conclusions Our data show that the level of salt‐induced H2O2 production negatively regulates RPTC sodium transport and determines the state of salt sensitivity in 2 strains of mice. High concentrations of antioxidants could prevent H2O2 production in renal proximal tubules, which would result in sodium retention and increased blood pressure.

Background: Recent studies have indicated that the skin lymphatic system and interstitium may play a role in the pathophysiology of arterial hypertension (AH)., Objectives: We aimed to determine whether the set of pathway parameters described previously in rodents would allow for the distinction between hypertensive and normotensive patients., Material and Methods: Molecular and histopathological parameters from the skin and blood of patients with AH (AH group, n = 53), resistant AH (RAH group, n = 32) and control (C group, n = 45) were used, and a statistical multivariate bootstrap methodology combining partial least squares-discriminant analysis (PLS-DA) and selectivity ratio (SR) were applied., Results: The C vs RAH model presented the best prediction performance (AUC test = 0.90) and had a sensitivity and specificity of 73.68% and 83.33%, respectively. However, the parameters selected for the C vs AH group model were the most important for the pathway described in the rodent model, i.e., greater density of the skin lymphatic vessels (D2-40 expression) and greater number of macrophages (CD68 expression), higher expression of the messenger ribonucleic acid (mRNA) of nuclear factor of activated T cells 5 (NFAT5), vascular endothelial growth factor C (VEGFC) and podoplanin (PDPN) in the skin, greater concentration of hyaluronic acid (HA) in the skin, and lower serum concentration of VEGF-C., Conclusions: Our study suggests that the NFAT5/VEGF-C/lymphangiogenesis pathway, previously described in rodent studies, may also be present in human HA. Further experiments are needed to confirm our findings.

Aim. To assess the influence of combination of antihypertension therapy on the main structure-function myocardium condition of the left ventricle (LV), thickness of intima-media (IMT) in patients with refractory arterial hypertension depending on the phenomenon of salt-sensitivity.Material and methods. Totally, 192 patients included with RAH, that after assessment for salt-sensitivity were randomized to groups: 1st group — salt-sensitive patients, receiving inhibitor of angiotensinconverting enzyme (ACEi), dihydropiridine calcium antagonist (DCA), thiazide diuretic (TD) and direct renin inhibitor (DRI) aliskiren (subgroup 1A) or β-adrenoblocker (β-AB) (subgroup 1B); 2 group — salt-resistant patients, receiving ACEi, DCA, TD and aliskiren (subgroup 2A) or β-AB (subgroup 2B). At the baseline and in 48 weeks of treatment the echocardiographic study was performed.Results. Addition of DRI in 1A subgroup helped to reach target values of blood pressure (BP) in 43,3%, and in subgroup 2A — in 70,4% of patients. Usage of β-AB in subgroup 1B led to decrease of BP to target values in 54,3%, and in 2B subgroup — in 50% patients. Usage of DRI in salt-resistant patients helped significantly to regress the LV hypertrophy than in salt-sensitive. Increase of the number of persons with normalized geometry and diastolic function of the LV was comparable in both groups. Usage of β-AB in salt-sensitive and -resistant patients was followed by statistically more significant improvement of structural and functional condition of myocardium of the LV. Normalized geometry of the LV was registered significantly more commonly in slat-sensitive patients. The decrease of IMT was comparable at the background of the usage of both variants of therapy not depending from salt-sensitivity.Conclusion. Usage of DRI as combination therapy led to more significant in salt-resistant than in salt-sensitive patients, antihypertensive effect and LV hypertrophy regress. Prescription of β-AB was followed by BP decrease to target values in comparable number of patients in 1B and 2B subgroups, but had some advantages in hypertrophy regression and normalization of LV myocardium geometry in salt-sensitive patients comparing to salt-resistant.

Isolated systolic hypertension, the most common form of hypertension in the elderly, but also detectable among young and middle-aged subjects, is independently associated with higher risk of cardiovascular events and all-cause mortality. Among various pathophysiological changes associated with aging, excess body weight and insulin resistance may predispose to this type of hypertension. Overweight or frank obesity and their frequent companion insulin resistance could mediate the development of isolated systolic hypertension through increase in the renin-angiotensin-aldosterone system activity, in the sympathetic tone and in salt-sensitivity, all in turn leading to endothelial dysfunction, arterial stiffness and increase in blood pressure. This review will focus on this cluster of pathophysiological factors and on the mechanistic pathways whereby they may favor the development of isolated systolic hypertension. [ABSTRACT FROM AUTHOR]

The metabolic syndrome describes a clustering of risk factors-visceral obesity, dyslipidaemia, insulin resistance, and salt-sensitive hypertension-that increases mortality related to cardiovascular disease, type 2 diabetes, cancer, and non-alcoholic fatty liver disease. The prevalence of these concurrent comorbidities is ~ 25-30% worldwide, and metabolic syndrome therefore presents a significant global public health burden. Evidence from clinical and preclinical studies indicates that glucocorticoid excess is a key causal feature of metabolic syndrome. This is not increased systemic in circulating cortisol, rather increased bioavailability of active glucocorticoids within tissues. This review examines the role of covert glucocorticoid excess on the hypertension of the metabolic syndrome. Here, the role of the 11β-hydroxysteroid dehydrogenase enzymes, which exert intracrine and paracrine control over glucocorticoid signalling, is examined. 11βHSD1 amplifies glucocorticoid action in cells and contributes to hypertension through direct and indirect effects on the kidney and vasculature. The deactivation of glucocorticoid by 11βHSD2 controls ligand access to glucocorticoid and mineralocorticoid receptors: loss of function promotes salt retention and hypertension. As for hypertension in general, high blood pressure in the metabolic syndrome reflects a complex interaction between multiple systems. The clear association between high dietary salt, glucocorticoid production, and metabolic disorders has major relevance for human health and warrants systematic evaluation. [ABSTRACT FROM AUTHOR]

Cellulose hydrogels with quaternary ammonium (QA) groups were prepared via the etherification and cross-linking reaction. The structure of the functional hydrogels with QA groups was confirmed with FT-IR. Differential scanning calorimeter (DSC) analysis indicated that there was a large amount of free water in the hydrogels. The hydrogels showed salt-sensitivity behavior, and they also exhibited a strong antibacterial activity toward Escherichia coli.

The pH/glucose/salt-sensitivity of boronic acid-functionalized nanoparticles based on the complexation of poly(3-methacrylamido phenylboronic acid) (PMAPBA) and dextran were studied. The size and light scattering intensity ratio (I/I0) kept constant at pH 7.0 and 8.0. When the pH value was further increased in the range of 8.0-10, the size of the nanoparticles increased, and I/I0reduced. As the pH value increased above 10, the size and I/I0of the nanoparticles remained constant. The nanoparticles were sensitive to glucose, galactose, mannose, sucrose and lactose, and the sugar-responsive behavior was dependent on the pH values, nanoparticle concentrations and sugar configurations. Due to the charge screening effect of salt, the size increased as salt concentration increased from 0 to 15 mg/mL at pH 9.0, and the aggregation of the nanoparticles was found when salt concentration above 9.0 mg/mL at pH 7.0. [ABSTRACT FROM PUBLISHER]

Renal denervation has been shown to lower arterial pressure in some hypertensive patients, yet it remains unclear whether this is due to ablation of afferent or efferent renal nerves. To investigate the role of afferent renal nerves in arterial pressure regulation, previous studies have used methods that disrupt both renal and nonrenal afferent signaling. The present study was conducted to develop and validate a technique for selective ablation of afferent renal nerves that does not disrupt other afferent pathways. To do this, we adapted a technique for sensory denervation of the adrenal gland by topical application of capsaicin and tested the hypothesis that exposure of the renal nerves to capsaicin (renal-CAP) causes ablation of afferent but not efferent renal nerves. Renal-CAP had no effect on renal content of the efferent nerve markers tyrosine hydroxylase and norepinephrine; however, the afferent nerve marker, calcitonin gene-related peptide was largely depleted from the kidney 10 days after intervention, but returned to roughly half of control levels by 7 wk postintervention. Moreover, renal-CAP abolished the cardiovascular responses to acute pharmacological stimulation of afferent renal nerves. Renal-CAP rats showed normal weight gain, as well as cardiovascular and fluid balance regulation during dietary sodium loading. To some extent, renal-CAP did blunt the bradycardic response and increase the dipsogenic response to increased salt intake. Lastly, renal-CAP significantly attenuated the development of deoxycorticosterone acetate-salt hypertension. These results demonstrate that renal-CAP effectively causes selective ablation of afferent renal nerves in rats. [ABSTRACT FROM AUTHOR]

Investigations regarding hypertension and dietary sodium, both factors that influence stroke risk, have previously been limited to using genetically disparate treatment and control groups, namely the stroke-prone, spontaneously hypertensive rat and Wistar-Kyoto rat. In this investigation, we have characterized and compared cerebral vasoactive system adaptations following stroke in genetically identical, salt-induced hypertensive, and normotensive control mice. Briefly, ANP (C57BJ/6 × SV129 background) mice were fed chow containing either 0.8 % NaCl (NS) or 8.0 % NaCl (HS) for 7 weeks. Transient cerebral ischemia was induced by middle cerebral artery occlusion (MCAO). Infarct volumes were measured 24-h post-reperfusion and the mRNA expression of five major vasoactive systems was characterized using qPCR. Along with previous publications, our data validate a salt-induced hypertensive state in ANP mice fed HS chow as they displayed left ventricular hypertrophy, increased systolic blood pressure, and increased urinary sodium excretion. Following MCAO, mice fed HS exhibited larger infarct volumes than their dietary counterparts. In addition, significant up-regulation in Et- 1 and Nos3 mRNA expression in response to salt and stroke suggests implications with increased cerebral damage in this group. In conclusion, our data demonstrate increased cerebral susceptibility to stroke in salt-induced hypertensive mice. More importantly, however, we have characterized a novel method of investigating hypertension and stroke with the use of genetically identical treatment and control groups. This is the first investigation in which genetic confounding variables have been eliminated. [ABSTRACT FROM AUTHOR]

Salt-sensitive individuals show earlier and more serious cardiac damage than nonsalt-sensitive ones. Some studies have suggested that microRNA-133a could reduce cardiac hypertrophy and myocardial fibrosis. The current study aims to investigate the different functions of high-salt intake on salt-sensitive (SS) rats and Sprague-Dawley (SD) rats and the involvement of microRNA-133a in these roles. After high-salt intervention, the left ventricular mass (LVW) and left ventricular mass index (LVMI) of the salt-sensitive high salt (SHS) group were obviously higher than those of the salt-sensitive low salt (SLS) group. However, the difference between the Sprague-Dawley high salt (DHS) group and the Sprague-Dawley low salt (DLS) group was not significant. Compared with SLS group, collagen I and connective tissue growth factor (CTGF) in the heart of SHS group were significantly higher, whereas no statistical difference was observed between the DHS group and the DLS group. Compared with low-salt diet, microRNA-133a in the heart of both strains were significantly decreased, but that in the SHS group decreased more significantly. These results suggest that high salt intervention could down-regulate the expression of myocardial microRNA-133a, which may be one of the mechanisms involved in myocardial fibrosis in salt-sensitive hypertension. [ABSTRACT FROM AUTHOR]

The kidney is the central pivot in the pathogenesis of hypertension. The future belongs to the personalized therapy of hypertension, related with the salt-sensitivity, natriuretic capacity and also with the volemic variations. Objectives. Demonstrating the importance of sodium diet in essential hypertension by altering echocardiographic parameters and underlining the most important mechanism for blood pressure regulating by kidney, represented of pressure natriuresis with revealing a correlation between level of natriuresis and blood pressure natriuresis and diet. Method. We performed a prospective open study in Nephrology Department of „St. John” Emergency Hospital, on 200 patients with essential hypertension stages 1 and 2 and we monitored the blood pressure values and natriuresis level according to salt intake, variability of blood pressure according to natriuresis and echocardiographic changes depending on the level of salt intake and of appropriate spontaneous natriuresis. Conclusions. The results demonstrate the importance of measuring natriuresis to prove the type of saltsensitivity of each patient, determining correlations between natriuresis and blood pressure values in assigning the level of natriuretic capacity disorder, cardiac output determination for establish indication for diuretic as first-line treatment. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To determine the effect of gestational hypertension on the developmental origins of blood pressure (BP), altered kidney gene expression, salt-sensitivity and cardiac hypertrophy (CH) in adult offspring. Methods: Female mice lacking atrial natriuretic peptide (ANP−/−) were used as a model of gestational hypertension. Heterozygous ANP+/− offspring was bred from crossing either ANP+/+ females with ANP−/− males yielding ANP+/−WT offspring, or from ANP−/− females with ANP+/+ males yielding ANP+/−KO offspring. Maternal BP during pregnancy was measured using radiotelemetry. At 14weeks of age, offspring BP, gene and protein expression were measured in the kidney with real-time quantitative PCR, receptor binding assay and ELISA. Results: ANP+/−KO offspring exhibited normal BP at 14weeks of age, but displayed significant CH (P<0.001) as compared to ANP+/−WT offspring. ANP+/−KO offspring exhibited significantly increased gene expression of natriuretic peptide receptor A (NPR-A) (P<0.001) and radioligand binding studies demonstrated significantly reduced NPR-C binding (P=0.01) in the kidney. Treatment with high salt diet increased BP (P<0.01) and caused LV hypertrophy (P<0.001) and interstitial myocardial fibrosis only in ANP+/−WT and not ANP+/−KO offspring, suggesting gestational hypertension programs the offspring to show resistance to salt-induced hypertension and LV remodeling. Our data demonstrate that altered maternal environments can determine the salt-sensitive phenotype of offspring. [Copyright &y& Elsevier]

Nitric oxide is a pronatriuretic and prodiuretic factor. The highest renal NO synthase (NOS) activity is found in the inner medullary collecting duct. The collecting duct (CD) is the site of daily fine-tune regulation of sodium balance, and led us to hypothesize that a CD-specific deletion of NOS1 would result in an impaired ability to excrete a sodium load leading to a salt-sensitive blood pressure phenotype. We bred AQP2-CRE mice with NOS1 floxed mice to produce flox control and CD-specific NOS1 knockout (CDNOS1KO) littermates. CDs from CDNOS1KO mice produced 75% less nitrite, and urinary nitrite+nitrate (NOx) excretion was significantly blunted in the knockout genotype. When challenged with high dietary sodium, CDNOS1KO mice showed significantly reduced urine output, sodium, chloride, and NOx excretion, and increased mean arterial pressure relative to flox control mice. In humans, urinary NOx is a newly identified biomarker for the progression of hypertension. These findings reveal that NOS1 in the CD is critical in the regulation of fluid-electrolyte balance, and this new genetic model of CD NOS1 gene deletion will be a valuable tool to study salt-dependent blood pressure mechanisms. [ABSTRACT FROM AUTHOR]

Backgroundgp91PHOX, a catalytic subunit of NAD(P)H oxidase, is involved in angiotensin II (Ang II)-induced superoxide (O2−) generation. This study was designed to examine the hypothesis that an enhancement in O2− generation due to elevated Ang II induces salt-sensitivity, which contributes to the development of hypertension.MethodsAssessment of blood pressure and renal excretory responses to Ang II infusion (2.2 ng·min/g) for 2 weeks via osmotic minipump was made in knockout (KO; n = 20) mice lacking the gene for gp91PHOX which were fed on either normal-salt (NS; 0.04% NaCl) or high-salt (HS, 4% NaCl) diet and compared these responses with those in wild-type (WT; n = 23) mice.ResultsAng II induced increase in systolic blood pressure (SBP) was started within the 4th day in all groups except in HS fed KO mice in which SBP increased after the 10th day of Ang II infusion. The increases in SBP were lower in KO than WT mice at the end of 2-week infusion period. In Ang II + HS fed KO mice, the urinary excretion rate of nitrite/nitrate (UNOxV) markedly increased but 8-isoprostane excretion rate remained unchanged. These findings indicate that an increase in nitric oxide (NO) with a lack of O2− formation was involved in the delayed hypertension in Ang II + HS fed KO mice.ConclusionThese data suggest that an enhanced O2− activity and its interaction with NO contribute to the early developmental phase of Ang II-induced salt-sensitive hypertension.American Journal of Hypertension (2011). doi:10.1038/ajh.2010.173 [ABSTRACT FROM AUTHOR]

Abstract: Endogenous cardiotonic steroids (CTS), also called digitalis like factors, have been postulated to play important roles in pathogenesis of hypertension for nearly half of a century. For the past 50years biomedical scientists have been in quest of an unidentified factor or hormone that both increases blood pressure and renal sodium excretion; this “natriuretic hormone” was, in fact, postulated to interact with the Na/K-ATPase. Recent discoveries have led to the identification of steroid molecules which are present in humans, rodents and amphibians, and which, in a complex manner, interact with each other and with the other systems that regulate renal salt handling and contribute to the salt-sensitivity of blood pressure. Recent findings include the specific identification of endogenous cardenolide (endogenous ouabain) and bufadienolide (marinobufagenin) CTS in humans along with the delineation of mechanisms by which CTS can signal through the Na/K-ATPase. Although CTS were first considered important in the regulation of renal sodium transport and arterial pressure, more recent work implicates these hormones in the central regulation of blood pressure and regulation of cell growth, and development of cardiovascular and renal fibrosis in particular. [ABSTRACT FROM AUTHOR]

Abstract: The ingestion of excess dietary salt (defined as NaCl) is strongly correlated with cardiovascular disease, morbidity, mortality, and is regarded as a major contributing factor to the pathogenesis of hypertension. Although several mechanisms contribute to the adverse consequences of dietary salt intake, accumulating evidence suggests that dietary salt loading produces neurogenically-mediated increases in total peripheral resistance to raise arterial blood pressure (ABP). Evidence from clinical studies and experimental models clearly establishes a hypertensive effect of dietary salt loading in a subset of individuals who are deemed “salt-sensitive”. However, we will discuss and present evidence to develop a novel hypothesis to suggest that while chronic increases in dietary salt intake do not elevate mean ABP in “non-salt-sensitive” animals, dietary salt intake does enhance several sympathetic reflexes thereby predisposing these animals and/or individuals to the development of salt-sensitive hypertension. Additional evidence raises an intriguing hypothesis that these enhanced sympathetic reflexes are largely attributed to the ability of excess dietary salt intake to selectively enhance the excitability of sympathetic-regulatory neurons in the rostral ventrolateral medulla. Insight into the cellular mechanisms by which dietary salt intake alters the responsiveness of RVLM circuits will likely provide a foundation for developing new therapeutic approaches to treat salt-sensitive hypertension. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009. [Copyright &y& Elsevier]

The renal pressure-natriuresis mechanism is the dominant controller of body fluid balance and long-term arterial pressure. In recent years, it has become clear that the balance of reactive oxygen and nitrogen species within the renal medullary region is a key determinant of the set point of the renal pressure-natriuresis curve. The development of renal medullary oxidative stress causes dysfunction of the pressure-natriuresis mechanism and contributes to the development of hypertension in numerous disease models. The purpose of this review is to point out the known mechanisms within the renal medulla through which reactive oxygen and nitrogen species modulate the pressure-natriuresis response and to update the reader on recent advances in this field. [ABSTRACT FROM AUTHOR]

In this study we examined the short- and long-term impact of early life dietary sodium (Na) on prenatally programmed hypertension. Hypertension was induced in rat offspring by a maternal low protein (LP) diet. Control and LP offspring were randomized to a high (HS), standard (SS), or low (LS) Na diet after weaning. On the SS diet, the LP pups developed hypertension by 6 weeks of age. The development of hypertension was prevented by the LS diet and exacerbated by the HS diet. Kidney nitrotyrosine content, a measure of oxidative stress, was reduced by the LS diet compared with the HS diet. The modified diets had no effect on control pups. A group of animals on the SS diet was followed up to 51 weeks of age after an early life 3-week exposure to the HS or LS diet. This brief early exposure of LP animals to the LS diet prevented the later development of hypertension and ameliorated the nephrosclerosis observed after early exposure to the HS diet. The LP offspring with early exposure to LS diet had lost their salt-sensitivity when challenged with the HS diet at the age of 43–49 weeks. No effect of early life dietary Na was observed in control animals. These results show that hypertension in this model is salt sensitive and may, in part, be mediated by salt-induced renal oxidative stress and that there may exist a developmental window which allows postnatal “reprogramming” of the hypertension. [ABSTRACT FROM AUTHOR]

Essential hypertension is the main cause of cardiovascular mortality and morbidity in the whole world, and especially in the industrial states, having a continuous increasing rate. The kidney is the central pivot in the pathogenesis of hypertension, due both to the deterioration of pressure-natriuresis and to the secretion of renin, its role being related to the genetic idiosyncrasy. For the moment, the clinical studies offer limited solutions, but the future belongs to the personalized therapy, related with the salt-sensitivity, genetic determinism of the natriuretic capacity and also with the importance of the volemic variations. [ABSTRACT FROM AUTHOR]

New amphoteric hydrogels based on carboxyethylchitosans (CECH) with various degrees of substitution (DS) were prepared using different amounts of epichlorohydrin (ECH) as the crosslinking agent. The equilibrium swelling ratio (SW) was determined as functions of pH and salt concentration. The hydrogels show typical amphoteric character responding to pH change of the external medium. At isoelectric point (IEP), the hydrogels shrink. The DS value has important effect on the swelling properties of the hydrogels. When the DS of N-carboxyethylchitosan increases from 0.32 to 0.72, the equilibrium swelling ratio (SW) of the hydrogel changes from 76 to 290 at pH 7.3 and from 117 to 499 at pH 11.3. A marked volume decrease was observed in hydrogels with increasing salt concentration in the surrounding solution. The viscoelastic properties of the hydrogels were studied by oscillatory shear measurements under small-deformation conditions. The elastic modulus G' of all the samples has no dependence on frequency and is one order of magnitude larger than the loss modulus G", corresponding to a strong gel behavior. [ABSTRACT FROM AUTHOR]

Abstract: The improvement of salt-sensitive hypertension is a therapeutic target for various vascular diseases. Glucagon-like peptide 1 (GLP-1), an incretin peptide, has been reported to have natriuretic effect as well as blood glucose lowering effect, although its exact mechanism and clinical usefulness remain unclear. Here, we examined anti-hypertensive effect of exendin-4, a GLP-1 analog, in salt-sensitive obese db/db mice and angiotensin II (angII)-infused C57BLK6/J mice. The treatment of exendin-4 for 12 weeks inhibited the development of hypertension in db/db mice. In db/db mice, the urinary sodium excretion was delayed and blood pressure was elevated in response to a high-salt load, whereas these were attenuated by exendin-4. In db/db mice, intra-renal angII concentration was increased. Furthermore, exendin-4 prevented angII-induced hypertension in non-diabetic mice and inhibited angII-induced phosphorylation of ERK1/2 in cultured renal cells. Considered together, our results indicate that exendin-4 has anti-hypertensive effects through the attenuation of angII-induced high-salt sensitivity. [Copyright &y& Elsevier]

The goal of this study was to test the hypothesis that increases in oxidative stress in Dahi S rats on a high-salt diet help to stimulate renal nuclear factor-κB (NF-κB), renal proinflammatory cytokines, and chemokines, thus contributing to hypertension, renal damage, and dysfunction. We specifically studied whether antioxidant treatment of Dahi S rats on high Na intake would decrease renal inflammation and thus attenuate the hypertensive and adverse renal responses. Sixty-four 7- to 8-wk-old Dahi S or R/Rapp strain rats were maintained for 5 wk on high Na (8%) or high Na + vitamins C (1 g/1 in drinking water) and E (5,000 IU/kg in food). Arterial and venous catheters were implanted at day 21. By day 35 in the high-Na S rats, antioxidant treatment significantly increased the renal reduced-to-oxidized glutathione ratio and decreased renal cortical H2O2 and O2·- release and renal NF-κB. Antioxidant treatment with vitamins C and E in high-Na S rats also decreased renal monocytes/macrophages in the glomeruli, cortex, and medulla, decreased tumor necrosis factor-α by 39%, and decreased monocyte chemoattractant protein-1 by 38%. Vitamin-treated, high-Na S rats also experienced decreases in arterial pressure, urinary protein excretion, renal tubulointerstitial damage, and glomerular necrosis and increases in glomerular filtration rate and renal plasma flow. In conclusion, antioxidant treatment of high-Na Dahi S rats decreased renal inflammatory cytokines and chemokines, renal immune cells, NF-κB, and arterial pressure and improved renal function and damage. [ABSTRACT FROM AUTHOR]

Abstract: Endogenous inhibitors of the Na/K-ATPase (NKA) and diabetes mellitus (DM) are both risk factors for preeclampsia and NaCl sensitive hypertension. Our goal was to test the hypothesis that NaCl supplementation, induces preeclampsia-like symptoms in pregnant rats with DM via stimulation of marinobufagenin (MBG), a natriuretic and vasoconstrictor inhibitor of the NKA. Type 2 DM in female Sprague–Dawley rats was induced by administration of 65mg/kg streptozotocin at day 4 post-partum. In intact rats, pregnancy was associated with a twofold increase in MBG levels and a mild impairment in glucose tolerance. Pregnant rats with DM exhibited fetal macrosomia, greater impairment of glucose tolerance, and higher levels of MBG as compared to that in normal pregnant rats. As compared to intact pregnant rats, NaCl supplementation of diabetic pregnant rats (drinking 1.8% NaCl during days 12–19 of pregnancy) was associated with an increase in systolic blood pressure, decreased fetal and placental weight, fivefold elevation of MBG excretion, and 42% inhibition of NKA in erythrocytes. In nonpregnant rats, in vivo pretreatment with anti-MBG antibody produced an exaggerated response of plasma levels of glucose and insulin in oral glucose tolerance test. These results suggest that MBG is a common factor in the pathogenesis of DM and preeclampsia, and that regulation of glucose tolerance may be one of the physiological functions of endogenous cardiotonic steroids. [Copyright &y& Elsevier]

1. Enhanced superoxide ( ) activity as a result of the inhibition of the superoxide dismutase (SOD) enzyme results in vasoconstrictor and antinatriuretic responses in the canine kidney; these responses were shown to be greatly enhanced during inhibition of nitric oxide synthase (NOS). Glomerular filtration rate remained mostly unchanged during SOD inhibition in the intact nitric oxide (NO) condition, but was markedly reduced during NOS inhibition. These findings indicate that endogenous NO has a major renoprotective effect against by acting as an anti-oxidant. Nitric oxide synthase inhibition was also shown to enhance endogenous activity. 2. Experiments in our laboratory using dogs, rats and gene knockout mice have shown that renal vasoconstrictor and antinatriuretic responses to acute or chronic angiotensin (Ang) II administration are mediated, in part, by generation. In the absence of NO, enhanced activity largely contributes to AngII-induced renal tubular sodium reabsorption. Acute or chronic treatment with the scavenger tempol in experimental models of hypertension (induced by chronic low-dose treatment with AngII and NO inhibitors) causes an improvement in renal haemodynamics and in excretory function, abolishes salt sensitivity and reduces blood pressure. 3. The present mini review also discusses related studies from many other laboratories implicating a role for and its interaction with NO in the development of salt-sensitive hypertension. 4. Overall, the collective data support the hypothesis that an imbalance between the production of NO and in the kidney primarily determines the condition of oxidative stress that alters renal haemodynamics and excretory function leading to sodium retention and, thus, contributes to the development of salt-sensitive hypertension. [ABSTRACT FROM AUTHOR]

The objective of this research was to examine the contribution of a moderately high fat (MHF) diet to the development of salt-sensitive hypertension in obese Zucker rats. Lean and obese Zucker rats were fed either a MHF diet or a diet of standard rat chow (control diet) for 10 weeks. From week 4 through week 10, the drinking water was supplemented with 1% NaCl. Blood pressure was measured weekly, and urinary excretion of nitric oxide metabolites (NOx) was determined at weeks 4 and 10. At week 10, renal nitric oxide synthase (NOS) activity was assessed in kidney homogenates. Blood pressures of obese, but not lean, rats on the MHF fat diet were significantly increased by salt-supplementation, whereas blood pressures of rats on the control diet were not appreciably affected. NOx excretion was increased in response to salt-supplementation in rats on the control diet, with the effect being particularly dramatic in obese rats. After salt-supplementation, NOx excretion by rats on the MHF diet was lower than rats on the control diet. In obese rats on the MHF diet, this decrease in NO production was accompanied by a reduction in renal NOS activity. These results indicate that obese rats are more inclined than lean rats to develop diet-induced hypertension in response to a moderately high fat, salt-supplemented diet. Furthermore, they suggest that MHF diet-induced defects in NO production may promote the salt-sensitivity of blood pressure in obese Zucker rats, which appear to require more NO to maintain blood pressure during a salt challenge. [ABSTRACT FROM AUTHOR]