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Increasing evidence suggests that hydrogen sulfide (H 2 S) is involved in brain mechanisms regulating the functions of the circulatory system. This appears to be mediated by cardiovascular centers located in the central nervous system. This chapter describes techniques of acute and chronic infusions into the brain cardiovascular centers in rats. Rats may be implanted either acutely or chronically with a cannula inserted into a selected cardiovascular center according to the stereotaxic coordinates. The cannula allows for the administration of the investigated compounds into a selected cardiovascular center.

Unlabelled: Accumulating evidence suggests that the brain renin-angiotensin system and proinflammatory cytokines, such as TNF-α, play a key role in the neurohormonal activation in chronic heart failure (HF). In this study we tested the involvement of TNF-α and angiotensin type 1 receptors (AT1Rs) in the central control of the cardiovascular system in HF rats., Methods: we carried out the study on male Sprague-Dawley rats subjected to the left coronary artery ligation (HF rats) or to sham surgery (sham-operated rats). The rats were pretreated for four weeks with intracerebroventricular (ICV) infusion of either saline (0.25μl/h) or TNF-α inhibitor etanercept (0.25μg/0.25μl/h). At the end of the pretreatment period, we measured mean arterial blood pressure (MABP) and heart rate (HR) at baseline and during 60min of ICV administration of either saline (5μl/h) or AT1Rs antagonist losartan (10μg/5μl/h). After the experiments, we measured the left ventricle end-diastolic pressure (LVEDP) and the size of myocardial scar., Results: MABP and HR of sham-operated and HF rats were not affected by pretreatments with etanercept or saline alone. In sham-operated rats the ICV infusion of losartan did not affect MABP either in saline or in etanercept pretreated rats. In contrast, in HF rats the ICV infusion of losartan significantly decreased MABP in rats pretreated with saline, but not in those pretreated with etanercept. LVEDP was significantly elevated in HF rats but not in sham-operated ones. Surface of the infarct scar exceeded 30% of the left ventricle in HF groups, whereas sham-operated rats did not manifest evidence of cardiac scarring., Conclusions: our study provides evidence that in rats with post-infarction heart failure the regulation of blood pressure by AT1Rs depends on centrally acting endogenous TNF-α., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

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 © 2014 Elsevier Ltd. All rights reserved.)

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 © 2012 Elsevier Ltd. All rights reserved.)

A number of neurotransmitters, including biologically active gases namely, nitric oxide (NO), hydrogen sulfide (H2S) and carbon monoxide (CO) have been postulated to play an important role in the control of the cardiovascular system by the brain. The attention of researchers has been focused on NO in particular. It has been shown that pharmacological manipulation of NO concentration in the brain produces significant changes in circulatory parameters. Furthermore, significant alterations in the brain NO system have been found in animal models of human cardiovascular diseases. These findings imply that NO in the brain may become a promising target for new treatment strategies. Although H2S and CO have also been proved to serve as transmitters in the central nervous system, their role in the neurogenic regulation of the cardiovascular system remains more obscure. Interestingly, increased synthesis of NO, H2S and CO is found in inflammation and it appears that the gases mediate some of the circulatory responses to inflammatory stimuli. In this review we discuss the role of brain gaseous transmitters in the control of the circulatory system in health and disease.

Accumulating evidence points to a pivotal role of the brain in the regulation of the circulatory system and energy balance. It has also been found that common civilization diseases such as depression, obesity, hypertension, myocardial infarction or heart failure are accompanied by an increase in concentration of inflammatory mediators in the blood, cerebrospinal fluid and various tissues. Recent studies have revealed that inflammatory mediators that are synthesized peripherally or in the brain may affect the nervous regulation of animal body systems. For example, it has been found that non-specific pro-inflammatory stimuli as well as treatment with several cytokines may cause depressive behavior, disturbances in energy balance and alterations in the circulatory system. On the other hand, knockout of genes for pro-inflammatory cytokines or administration of anti-inflammatory mediators may normalize the pathological changes. In the present manuscript we will review studies that imply the common neuroinflammatory pathogenesis of cardiovascular diseases, depression and energy balance disorders.

Background: Angiotensin 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., Methods: Twelve-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., Results: ICV 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., Conclusions: The 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.

Recently, it was found that hydrogen sulfide (H2S) may serve as an important transmitter in peripheral organs as well as in the brain. The aim of the present study was to evaluate the possible function of H2S in the brain regulation of the circulatory system. Experiments were performed on conscious, male, Wistar-Kyoto rats. Mean arterial blood pressure (MABP) and heart rate (HR) were recorded continuously under baseline conditions and during infusions into the lateral cerebral ventricle (LCV) of the experimental animals. In control series LCV infusion of vehicle (Krebs-Henseleit bicarbonate-buffer) did not cause significant changes in MABP or HR. LCV infusion of H2S donor (NaHS) at the rate of 400 n/h resulted in an increase in MABP, whereas infusions at the rate of 100 n/h and 200 n/h failed to change MABP. On the other hand LCV infusion of H2S donor at the rate of 200 n/h caused a significant increase in HR while infusion at the rate of 400 n/h produced an increase in HR, which was smaller than this observed during infusion at the rate of 200 n/h. H2S donor administered at the rate of 100 n/h failed to affect HR. In conclusion, the present study demonstrates that exogenous hydrogen sulfide changes hemodynamic parameters by centrally mediated mechanisms. The hemodynamic effect seems to be dependent on H2S concentration in cerebrospinal fluid. It appears that the hypertensive response may occur at a concentration, which does not exceed twice the physiological level.

The present study was designed to find out whether brain nitric oxide (NO) influences hemodynamic response to intracerebroventricular (ICV) infusion of interleukin-1 beta (IL-1beta). Mean arterial blood pressure (MAP) and heart rate (HR) were recorded in seven series of experiments performed on conscious Sprague-Dawley rats receiving during 60 min ICV infusion of: 0.9% NaCl (5 microl/h; series 1), IL-1beta (100 ng/h; series 2), NO synthase inhibitor (L-NAME, 1mg/h; series 3), IL-1beta together with L-NAME (series 4), IL-1beta together with inactive isomer of NO synthase inhibitor (D-NAME, 1mg/h; series 5), NO donor (SNAP, 40 microg/h; series 6) and IL-1beta together with SNAP (series 7). ICV infusion of saline did not influence MAP while administration of IL-1beta as well as IL-1beta together with D-NAME elicited a significant, though transient, increase in MAP. In series 4, combined infusion of IL-1beta and L-NAME exerted an increase in MAP, which persisted until the end of the experiment and was significantly higher than in series 2 and 5. In series 7, infusion of SNAP together with IL-1beta abolished the pressor effect of IL-1beta. HR was not significantly altered in any of the experimental series. These results demonstrate that inhibition of NO synthesis in the brain enhances and prolongs the pressor response to IL-1beta, whereas concomitant administration of NO donor abolishes the hemodynamic effect of IL-1beta. Therefore, we conclude that NO generated in the brain is involved in buffering the pressor response to IL-1beta.

Accumulating evidence points to a pivotal role of the brain in the regulation of the circulatory system and energy balance. It has also been found that common civilization diseases such as depression, obesity, hypertension, myocardial infarction or heart failure are accompanied by an increase in concentration of inflammatory mediators in the blood, cerebrospinal fluid and various tissues. Recent studies have revealed that inflammatory mediators that are synthesized peripherally or in the brain may affect the nervous regulation of animal body systems. For example, it has been found that non-specific pro-inflammatory stimuli as well as treatment with several cytokines may cause depressive behavior, disturbances in energy balance and alterations in the circulatory system. On the other hand, knockout of genes for pro-inflammatory cytokines or administration of anti-inflammatory mediators may normalize the pathological changes. In the present manuscript we will review studies that imply the common neuroinflammatory pathogenesis of cardiovascular diseases, depression and energy balance disorders. [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]