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Research suggests that statins affect the regulation of arterial blood pressure (BP), however, the mechanisms remain obscure. We maintained male, 12–week–old, Sprague–Dawley rats on tap water (controls) or water containing simvastatin or pravastatin for 4 weeks. Subsequently, we measured mean arterial blood pressure and heart rate at baseline and after intravenous infusion of either saline or angiotensin II (Ang II). Additionally, we tested baroreflex function and the effect of statins on vasoconstrictor response to Ang II on isolated femoral artery branches. Controls and simvastatin and pravastatin groups showed a significant increase in mean arterial BP and heart rate in response to Ang II. The increase was significantly smaller in the simvastatin group than in controls and in the pravastatin group. In contrast, when pretreated with hexamethonium, a ganglionic blocker, simvastatin and pravastatin groups showed a similar hypertensive response to Ang II, which was smaller than in controls. Likewise, the Ang II–induced vasoconstrictor response of femoral artery branches was comparable between simvastatin and pravastatin groups and smaller than in controls. We found no effect of statins on the baroreflex. This study shows that simvastatin and pravastatin differ in their effects on the Ang II–dependent mechanisms controlling BP. [ABSTRACT FROM AUTHOR]

Recent studies suggest that blood-borne metabolites of gut microbiota, such as trimethylamine N-oxide (TMAO) are involved in the aetiology of cardiovascular diseases and may serve as markers of cardiovascular risk. To enter the bloodstream the microbiota-derived molecules need to pass the gut-blood barrier (GBB). The GBB plays an important role in maintaining organism homeostasis. It is a complex multi-layer system which determines the absorption of nutrients, water and many other substances. The integrity and permeability of the GBB may be impaired in numerous diseases including gastrointestinal, metabolic and cardiovascular diseases. Here, we propose that the evaluation of the GBB permeability may have a significant diagnostic potential in cardiovascular and metabolic diseases. Second, we suggest that the GBB permeability is a variable that confounds diagnostic value of new gut microbiota-derived biomarkers such as TMAO. Therefore, cardiovascular risk assessment requires the evaluation of both TMAO and the GBB permeability. [ABSTRACT FROM AUTHOR]

Abstract: Accumulating evidence suggests that blood borne hormones modulate brain mechanisms regulating blood pressure. This appears to be mediated by the circumventricular organs which are located in the walls of the brain ventricular system and lack the blood–brain barrier. Recent evidence shows that neurons of the circumventricular organs express receptors for the majority of cardiovascular hormones. Intracerebroventricular infusions of hormones and their antagonists is one approach to evaluate the influence of blood borne hormones on the neural mechanisms regulating arterial blood pressure. Interestingly, there is no clear correlation between peripheral and central effects of cardiovascular hormones. For example, angiotensin II increases blood pressure acting peripherally and centrally, whereas peripherally acting pressor catecholamines decrease blood pressure when infused intracerebroventricularly. The physiological role of such dual hemodynamic responses has not yet been clarified. In the paper we review studies on hemodynamic effects of catecholamines, neuropeptide Y, angiotensin II, aldosterone, natriuretic peptides, endothelins, histamine and bradykinin in the context of their role in a cross-talk between peripheral and brain mechanisms involved in the regulation of arterial blood pressure. [Copyright &y& Elsevier]

Abstract: Hypertension is a chronic medical condition in which systemic arterial blood pressure is elevated. About 80–90% of diagnosed hypertension is considered essential (idiopathic), which means there is no obvious cause of the increase in blood pressure. My hypothesis states that part of idiopathic hypertension results from erroneous information that the brain receives from receptors involved in the regulation of arterial blood pressure, i.e. if, despite high systemic blood pressure, the brain receives false “low-arterial pressure input” from cardiovascular receptors. As a result the brain centres which control blood pressure reset and produce an inappropriate output to the effectors (heart, blood vessels, kidneys and glands). The information errors may result from: (i) structural and/or functional impairment of cardiovascular receptors, (ii) changes in cardiovascular receptors activity, which are caused by other factors than changes in blood pressure, and (iii) impaired transmission in afferent fibres. I assume that in contrast to the lack of input from damaged or denervated cardiovascular receptors, an erroneous input will impair the control of arterial blood pressure. This will apply especially to false input which imitates “low-arterial pressure input”. Higher priority of “low-arterial pressure input” over “high-arterial pressure input” or none input may be explained by the evolutionary adaptation, i.e. low blood pressure, mostly due to haemorrhage, used to be a more common condition than high blood pressure and constitute a major threat to humans. [Copyright &y& Elsevier]

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 objective of the present study was to find out whether brain vasopressin (AVP) and angiotensin II (Ang II) are involved in pressor response to intracerebroventricular (ICV) infusion of interleukin-1 beta (IL-1β). The experiments were performed on conscious, 12- to 14-week-old Sprague–Dawley rats. Mean arterial blood pressure (MAP) and heart rate (HR) were recorded continuously under baseline conditions and during ICV infusion periods. In the first part of the study, the rats were ICV-infused with one of the following: 0.9% NaCl saline (5 μl/h—control), IL-1β (100 ng/h), angiotensin AT1 receptor antagonist (losartan 10 μg/h), IL-1β together with losartan, V1 receptors antagonist (V1ANT), d(CH2)5[Tyr(Me)2,Ala-NH2 9]AVP, 400 ng/h) or IL-1β together with V1ANT. Saline infusion did not influence MAP, while administration of IL-1β elicited a significant but transient increase in MAP. The pressor response to IL-1β was abolished by losartan but not by V1ANT. On the other hand, combined administration of IL-1β and V1ANT resulted in increase in HR, which was absent during infusion of IL-1β alone. In the second part of the study after ICV pretreatment with IL-1β or 0.9% NaCl (control), the rats received ICV infusion of one of the following: 0.9% NaCl saline, subpressor dose of Ang II (5 ng/15 s) or subpressor dose of AVP (5 ng/15 s). Subpressor doses of Ang II and AVP did not influence MAP and HR in saline-pretreated rats. The same dose of Ang II but not AVP applied in IL-1β-pretreated rats resulted in a significant increase in MAP. The study provides evidence that IL-1β through its action in the brain increases sensitivity to central pressor action of Ang II. Additionally, we found that AVP and in particular V1 receptors do not play important role in the central pressor action of IL-1β, however, they may influence its effect on HR regulation. [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]

The prevalence of hypertension increases with age, but the mechanisms linking this phenomenon are not well understood. Hydrogen sulfide (H 2 S) may be involved in this process, as it plays a role in the cardiovascular system, affecting blood pressure and heart and kidney functions. The aim of this study was to evaluate the influence of hypertension and aging on sulfur-containing compounds metabolism in the hearts and kidneys of Wistar Kyoto (WKY) and Spontaneously Hypertensive Rats (SHR) of different age groups. We determined the expression and activity of four enzymes participating in H 2 S production: cystathionine beta-synthase (CBS), cystathionine gamma-lyase (CTH), 3-mercaptopyruvate sulfurtransferase (MPST), and thiosulfate sulfurtransferase (TST). The levels of reduced/oxidized glutathione, cysteine, cystine, and cystathionine, and the ability of tissues to form hydrogen sulfide were also investigated. Tissues obtained from younger WKY rats produced the highest amounts of H 2 S. The effect of hypertension on the metabolism of sulfur-containing compounds was manifested by a decrease in sulfane sulfur concentrations in heart homogenates and a decrease in CTH activity in the kidneys. The hearts and kidneys of older WKY rats were characterized by lower MPST or CTH gene expression, respectively, compared to younger animals. Our study demonstrates that hypertension and aging influence cardiac and renal sulfur-containing compounds metabolism and reduce H 2 S production. Furthermore, we showed that MPST plays a major role in the production of hydrogen sulfide in the heart and CTH in the kidneys of rats. • Hypertension and aging affect cardiac and renal sulfur metabolism in rats. • H 2 S production is decreased in heart and kidneys of hypertensive and older rats. • 3-mercaptopyruvate sulfurtransferase is responsible for H 2 S generation in rat heart. • Cystathionine gamma-lyase plays a major role in H 2 S formation in rat kidneys. [ABSTRACT FROM AUTHOR]

Dual antiplatelet therapy (DAPT) prevents ischemic events in patients with acute coronary syndrome (ACS), but is associated with increased risk of bleeding events. Symmetric dimethylarginine (SDMA) is one of nitric oxide (NO)-related pathway metabolites and stands as a promising biomarker of early chronic kidney disease (CKD) and cardiovascular diseases (CVDs). Our study evaluated the role of SDMA in predicting bleeding events in patients after ACS treated with DAPT. We compared plasma concentrations of NO-related pathway metabolites in patients with ACS (n = 291) and investigated the prognostic value of SDMA as a bleeding predictor during 1-year follow-up. We measured the metabolites concentration using ultra performance liquid chromatography. Platelet reactivity was determined using impedance aggregometry. Patients with the highest quartile (4th) of SDMA concentration had significantly lower platelet aggregation compared to those in the 1st-3rd quartiles of SDMA, based on ADP + PGE1-, AA-, and ADP-induced platelet reactivity tests (p = 0.0004, p = 0.002, p = 0.014, respectively). Patients with major or minor bleeding events had significantly higher concentrations of SDMA as compared to those without bleeding events or to those with minimal bleeding events (p = 0.019, p = 0.019, respectively). Higher SDMA concentration is associated with lower platelet reactivity and is associated with major and minor bleeding events in patients with ACS on DAPT. Therefore, SDMA stands as a potential biomarker for individualization of duration and potency of antiplatelet therapies in the ACS population at high risk of bleeding complications. • Dual antiplatelet therapy is a risk factor for major and minor bleeding events. • Higher SDMA concentration is associated with cardiovascular and chronic kidney disease. • We present association between SDMA and platelet reactivity. • Higher concentrations of SDMA were in patients with major or minor bleeding events. • SDMA is a potential biomarker of bleeding risk in patients on dual antiplatelet therapy. [ABSTRACT FROM AUTHOR]

Valeric acid (VA) is a short-chain fatty acid produced by microbiota and herbs such as Valeriana officinalis. Moreover, VA is released from medicines such as estradiol valerate by esterases. We evaluated the concentrations of endogenous VA in male, 14-week-old rats in the liver, heart, brain, kidneys, lungs, blood and in the colon, a major site of microbiota metabolism, using liquid chromatography coupled with mass spectrometry. In addition, the tissue distribution of VA D9-isotope (VA-D9) administered into the colon was assessed. Finally, we investigated the effect of exogenous VA on arterial blood pressure (BP) and heart rate (HR) in anesthetized rats, and the reactivity of mesenteric (MA) and gracilis muscle (GMA) arteries ex vivo. Physiological concentration of VA in the colon content was ≈650 μM, ≈ 0.1–1 μM in the investigated tissues, and ≈0.4 μM in systemic blood. VA-D9 was detected in the tissues 5 min after the administration into the colon. The vehicle did not affect BP and HR. VA produced a dose-dependent decrease in BP, and at higher doses lowered HR. The hypotensive effect of VA was inhibited by 3-hydroxybutyrate, an antagonist of GPR41/43-receptors but not by the subphrenic vagotomy. Hexamethonium prolonged the hypotensive effect of VA while atropine did not influence the hypotensive effect. VA dilated GMA and MA. In conclusion, the exogenous VA produces vasodilation and lowers BP. The colon-derived VA rapidly penetrates to tissues involved in the control of BP. Further studies are needed to evaluate the effects of endogenous and exogenous VA on the circulatory system. [ABSTRACT FROM AUTHOR]