Search

Introduction: Increased plasma level of trimethylamine N-oxide (TMAO), a bacterial metabolite of choline, is associated with an increased cardiovascular risk. Indoxyl sulfate, a bacterial metabolite of tryptophan, is thought to be associated with higher mortality in cardiorenal syndrome. We hypothesized that enalapril, a well-established drug reducing cardiovascular mortality, may affect the plasma level of gut bacteria-derived metabolites and gut bacteria composition. Materials and methods: 14-16-week-old Wistar rats were maintained either on water (controls) or water solution of enalapril for two weeks (5.3 or 12.6 mg/kg b.w.). Blood plasma and urine were analyzed for the concentration of TMAO and indoxyl sulfate using liquid chromatography coupled with triple-quadrupole mass spectrometry. Gut bacteria composition was analyzed with 16S rRNA gene sequence analysis. Results: Rats treated with enalapril showed a significantly lower plasma TMAO level and a trend towards higher 24 h urine excretion of TMA and TMAO. Plasma indoxyl level was similar between the groups. There was no significant difference between the groups in gut bacteria composition. Conclusions: Enalapril decreases rat plasma TMAO, but does not affect the plasma level of indoxyl sulfate and gut bacteria composition. The enalapril-induced decrease in plasma TMAO level may be of therapeutic and diagnostic importance. [ABSTRACT FROM AUTHOR]

Noninvasive hemodynamic measurements in rats require placing animals in restrainers. To minimize restraint stress-induced artifacts several habituation protocols have been proposed, however, the results are inconclusive. Here, we evaluated if a four-week habituation is superior to a shorter habituation, or no habituation. This is the first study comparing different habituation protocols with the use of four-week continuous telemetry measurements. We did the experiments on male, 16-week old, Sprague–Dawley rats. Continuous recordings of mean arterial blood pressure (MABP) and heart rate (HR) were made before and during habituation protocols. Rats were subjected either to control (four weeks of restraint-free recordings,n = 5) or two-week (seven restraints,n = 6) or four-week (14 restraints,n = 6) restraint sessions. The restraint protocols included placement of rats in the middle of the dark phase into plastic restrainers as used for tail-cuff measurements. Restraint lasted for 60 min, and was repeated every second day. Each restraint significantly increased MABP (by 15–25 mmHg) and HR (by 40–120 beats/min). Exposure to the restraint protocols decreased diurnal variation in MABP. There was no hemodynamic adaptation to repeated restraint, and no significant difference in hemodynamic response to restraint among controls, the two-week and the four-week groups. In conclusion, our study indicates that measurements in restrained rats are not likely being made without stress-induced changes in MABP. Moreover, in hemodynamic studies in repeatedly restrained rats longer habituation is not superior to shorter habituation. [ABSTRACT FROM PUBLISHER]

S-adenosyl- l-methionine (SAM) is an amino acid involved in a number of physiological processes in the nervous system. Some evidence suggests a therapeutic potential of SAM in hypertension. In this study we investigated the effect of intracerebroventricular (ICV) infusions of SAM on arterial blood pressure in rats. Mean arterial blood pressure (MABP) and heart rate (HR) were measured at baseline and during ICV infusion of either SAM or vehicle (aCSF; controls) in conscious, male normotensive Wistar Kyoto rats (WKY) and Spontaneously Hypertensive Rats (SHR). MABP and HR were not affected by the vehicle. WKY rats infused with SAM (10 μM, 100 μM and 1 mM) showed a biphasic hemodynamic response i.e., mild hypotension and bradycardia followed by a significant increase in MABP and HR. On the contrary, SHR infused with SAM showed a dose-dependent hypotensive response. In separate series of experiments, pretreatment with hexamethonium, a ganglionic blocker as well as pretreatment with glibenclamide, a K channel blocker reduced the hemodynamic effects of SAM. SAM may affect the nervous control of arterial blood pressure via the autonomic nervous system and K channel-dependent mechanisms. [ABSTRACT FROM AUTHOR]

A high-Na diet may lead to the development of hypertension in both humans and rats; however, the causes of Na intake in amounts greater than physiologically needed as well as the mechanisms whereby high-Na food elevates blood pressure are not clear. Therefore, we decided to test the hypothesis that a high-Na diet introduced after suckling affects Na intake, food preference, resting blood pressure and blood volume in adult rats. Male Wistar-Kyoto (WKY) rats, 4 weeks old, were divided into three groups and placed on either a high-Na (3·28%), a medium-Na (0·82%) or a regular diet (0·22%) with the same energy content for 8 weeks. Subsequently, food preference, resting arterial blood pressure, blood volume, plasma osmolality and Na blood level were evaluated. When offered a choice of diets, all the groups preferred the regular chow, and there was no significant difference in total Na intake between the groups. When the rats experienced the change from their initial chow to a new one with different Na content, they continued to eat the same amount of food. Body weight, resting arterial blood pressure, blood volume, plasma osmolality and Na blood level were comparable between the groups. In conclusion, the results show that a high-Na diet introduced immediately after suckling does not affect Na preference and Na intake in adult WKY rats. Furthermore, the findings provide evidence that both blood volume and arterial blood pressure are highly protected in normotensive rats on a high-Na diet. [ABSTRACT FROM PUBLISHER]

BackgroundAngiotensin II (Ang II) plays a pivotal role in regulation of the circulatory system. Activation of angiotensin type 1 (AT1) receptors in several brain regions leads to an increase in blood pressure. Accumulating data suggest that statins affect the peripheral action of Ang II; however, their central effects are poorly recognized. The study was aimed to determine whether simvastatin interferes with the brain angiotensin system in rats.MethodsTwelve-week-old, Sprague-Dawley rats were divided into two groups. Untreated group was maintained on tap water, whereas simvastatin group received water containing simvastatin for the following 12 weeks. Later, both groups were subjected to experiments in which mean arterial blood pressure (MABP) and heart rate (HR) were recorded during baseline conditions and after intracerebroventricular (ICV) infusion of either saline, Ang II, or losartan.ResultsICV infusion of Ang II elicited a significant increase in MABP in both groups. However, the pressor response in the simvastatin group was significantly smaller than that in the untreated group. There was no significant change in MABP after ICV infusion of saline or losartan. ICV infusion of Ang II elicited a significant increase in HR in the untreated group but not in the simvastatin group. There was no significant change in HR after ICV infusion of saline or losartan.ConclusionsThe results show that simvastatin reduces the pressor response to ICV-infused Ang II in rats. This implies that statins may affect the central regulation of the circulatory system, especially when the brain angiotensin system is stimulated.American Journal of Hypertension 2010; doi:10.1038/ajh.2010.103 [ABSTRACT FROM AUTHOR]

Abstract: The purpose of the present study was to establish the effect of chronic central interleukin-1 receptors blockade and central chronic infusion of interleukin-1 beta (IL-1β) on cardiovascular response to an acute stressor. The experiments were performed on 12–14-week-old, male WKY rats, divided into three experimental groups. Each group was subjected to chronic intracerebroventricular (ICV) infusion of one of the following compounds: saline (control, group C), recombinant rat IL-1 receptor antagonist (IL-ANT group) or interleukin-1 beta (IL-1B group). After 5 days of the ICV infusions mean arterial blood pressure (MABP) and heart rate (HR) were recorded continuously under baseline conditions and after the application of an air jet stressor. The stressor was applied three times with 10-min intervals. There were no significant differences in MABP and HR between groups under baseline conditions and immediately before the application of the three consecutive air jets. After the first stressor the IL-ANT group responded with a significantly lower increase in blood pressure than the control and IL-1B group. After the application of the two following air jets only the trend for an intergroup difference was present. The results of the present study provide further evidence that cytokines play an important role in the regulation of the circulatory system. The most important new finding is that the magnitude of the pressor response to the alarming stress is strongly influenced by IL-1 receptors in the brain. [Copyright &y& Elsevier]

Abstract: The aim of the present study was to evaluate the influence of intraventricular administration of recombinant rat interleukin-1β (IL-1β) on regulation of resting blood pressure and heart rate and to test the hypothesis that the brain angiotensinergic system is involved in regulation of hemodynamic parameters by centrally applied IL-1β. The experiments were performed on Sprague Dawley rats, assigned to three series of experiments. In series 1 (control, n =6), mean arterial pressure (MAP) and heart rate (HR) were recorded for 15min under baseline conditions. This was followed by infusion of saline (0.9% sterile NaCl 5μL/h) into the left cerebral ventricle (LCV). Measurements were continued during the next 60min. In series 2 (n =6) and 3 (n =6) the experimental design was similar, except that in series 2 the animals were LCV infused with saline containing IL-1β (100ng/h) and in series 3 with saline containing IL-1β (100ng/h) and angiotensin type 1 (AT1) receptors antagonist (Losartan, 10μg/h). LCV infusion of saline alone did not influence MAP and HR while administration of IL-1β elicited significant increase in MAP, but not in HR. The pressor effect was absent during combined infusion of IL-1β and Losartan. Results of the study provide evidence that centrally administered IL-1β exerts pressor effect, and reveal that this effect is mediated by stimulation of the brain angiotensin system and requires activation of AT1 receptors. [Copyright &y& Elsevier]

Hypertension and age are key risk factors for cardiovascular morbidity and mortality. Hydrogen sulfide (H2S), a gaseous transmitter, contributes significantly to regulating arterial blood pressure and aging processes. This study evaluated the effects of hypertension and aging on the hepatic metabolism of sulfur-containing compounds, the activity of the enzymes involved in sulfur homeostasis, and the liver's ability to generate H2S. Livers isolated from 16- and 60-week-old normotensive Wistar Kyoto rats (WKY) and Spontaneously Hypertensive Rats (SHR) were used to evaluate gene expression using RT-PCR, and the activity of enzymes participating in H2S metabolism, including thiosulfate sulfurtransferase (rhodanese; TST), cystathionine gamma-lyase (CTH), and 3-mercaptopyruvate sulfurtransferase (MPST). The levels of cysteine, cystine, reduced and oxidized glutathione were measured using RP-HPLC. SHR livers from both age groups showed a higher capacity to generate H2S than livers from WKY. The gene expression and activity of enzymes involved in sulfur metabolism differed between WKY and SHR, and between the age groups. For example, 16-week-old SHR had significantly higher activity of TST than 16-week-old WKY. Furthermore, differences between younger and older WKY rats in the expression and/or activity of TST and MPST were present. In conclusion, our study shows that arterial hypertension and aging affect hepatic sulfur metabolism and H2S production in rats. These findings pave the way for interventional studies evaluating a potential causal relation between liver sulfur metabolism, hypertension and aging. [ABSTRACT FROM AUTHOR]