Ewa Szczepanska-Sadowska

Interaction of vasopressin and angiotensin II in central control of blood pressure and thirst.

It is now well recognized that systemically released angiotensin II (Ang II) and arginine vasopressin (AVP) act in concert in regulation of blood pressure and water-electrolyte balance. Numerous studies have also demonstrated that centrally applied Ang II and AVP cause significant alterations of the cardiovascular functions and body fluid balance. Moreover, it has been established that Ang II and AVP are released in the central nervous system during cardiovascular and osmotic disorders and that the cardiovascular regions of the brainstem and the osmoregulatory regions of the forebrain are extensively innervated by the angiotensinergic and vasopressinergic neurons. Some evidence indicates that the angiotensinergic and vasopressinergic system may interact in the central blood pressure control, although the significance of this interaction may differ in various species. Recently, attempts have been made to find out whether centrally released Ang II and AVP may play a role in the regulation of the cardiovascular system under physiological and pathophysiological conditions. With regard to this, the available evidence strongly suggests that the both systems may be involved in regulation of blood pressure under baseline conditions. In addition, the vasopressinergic system appears to be involved in the adjustment of cardiovascular functions to hypovolemia, whereas its role in regulation of blood pressure during the osmotic disorders is less clear. Regulation of blood pressure and heart rate by centrally released AVP under baseline conditions, during hypovolemia and in osmotic disorders is significantly altered in the spontaneously hypertensive rats. It is now well established that centrally applied Ang II and Ang III are potent dipsogenic compounds. There also is evidence that AVP may enhance the osmotic thirst. However, the physiological role of brain-derived AVP and Ang II in the control of water intake awaits further examination. The available evidence from rat studies does not give support to a significant cooperation between central angiotensinergic and vasopressinergic system in regulation of water intake.

Enhanced involvement of brain vasopressin V1 receptors in cardiovascular responses to stress in rats with myocardial infarction

Stress is one of the factors provoking cardiovascular complications. The purpose of the study was to explore the role of vasopressin (VP) in central control of arterial blood pressure and heart rate under resting conditions and during stimulation by an alarming stress (air jet stress) in myocardial infarct-induced cardiac failure. Six groups of male Sprague Dawley (SD) rats were subjected either to sham surgery (sham rats) or to ligation of a left coronary artery (infarcted rats). After 5 weeks both infarcted and sham rats were subjected either to intracerebroventricular infusion of artificial cerebrospinal fluid (aCSF) (sham aCSF and infarcted aCSF), [Arg8]-VP (sham VP and infarcted VP) or VP V1a receptor antagonist (d(CH2)5[Tyr(Me)2Ala-]VP, sham V1ANT and infarcted V1ANT). Air jet stress elicited significantly greater increases in mean arterial blood pressure (MABP) and heart rate in the infarcted aCSF than in the sham aCSF rats. Intracerebroventricular infusion of V1ANT significantly reduced resting MABP and MABP and heart rate increases in response to stress in the infarcted but not in the sham rats. Intracerebroventricular infusion of VP elicited a significant increase in resting MABP in the infarcted VP but not in the sham VP rats. The results provide evidence for enhanced engagement of the brain V1 VP receptors in regulation of resting MABP and in generation of exaggerated cardiovascular responses to air jet stress during the post-infarct state.

Central oxytocin modulation of acute stress-induced cardiovascular responses after myocardial infarction in the rat.

The present study was aimed at determining the role of centrally released oxytocin in regulation of blood pressure and heart rate (HR) under resting conditions and during an acute air-jet stress in rats with a myocardial infarction and controls infarcted. Four weeks after ligation of a coronary artery or sham surgery, conscious Sprague Dawley rats were subjected to one of the following intracerebroventricular (ICV) infusions: (1) 0.9% NaCl (control), (2) oxytocin, (3) oxytocin receptor antagonist {desGly-NH2-d(CH2)5[D-Tyr2Thr4]OVT}(OXYANT). Resting arterial blood pressure and HR were not affected by any of the ICV infusions either in the infarcted or sham-operated rats. In the control experiments, the pressor and tachycardic responses to the air jet of infarcted rats were significantly greater than in the sham-operated rats. OXYANT significantly enhanced the cardiovascular responses to stress only in the sham-operated rats whereas oxytocin significantly attenuated both responses in the infarcted but not in the sham-operated rats. The results suggest that centrally released endogenous oxytocin significantly reduces the cardiovascular responses to the acute stressor in control rats. This buffering function of the brain-oxytocin system is not efficient during the post-myocardial infarction state, however it may be restored by central administration of exogenous oxytocin.

Interaction of AT1 receptors and V1a receptors-mediated effects in the central cardiovascular control during the post-infarct state.

UNLABELLED Experimental objectives. Because myocardial infarct is associated with overactivation of brain angiotensin II (ANG II) and vasopressin (AVP) V1a receptors we decided to determine whether AT1 and V1a receptors-mediated effects of ANG II and AVP interact in central cardiovascular control during the post-infarct state. Four groups of infarcted and four groups of sham-operated conscious rats entered the study. Results. In the infarcted rats cerebroventricular infusion of AT1 (AT1ANT, losartan) and V1a antagonist {V1aANT,d(CH(2))(5)[Tyr(Me)(2)Ala-NH(2)(9)]VP} and combined infusion of both these compounds performed 4 weeks after induction of the infarct significantly and comparably reduced mean arterial blood pressure (MABP) in comparison to control experiments (artificial cerebrospinal fluid infusion). In the sham rats MABP was not affected by any of the infusions. In control experiments MABP and HR responses to an alarming air jet stress were significantly higher in the infarcted than in the sham rats. Both responses were normalized with the same effectiveness by administration of AT1ANT, V1aANT and AT1ANT+V1aANT. In the sham rats administration of these compounds did not affect MABP and HR responses to stress. CONCLUSION The results provide evidence for interaction of AT1 and V1a receptors-mediated effects of ANG II and AVP in the central cardiovascular control during the post-infarct state.

Brain vasopressin V1 receptors contribute to enhanced cardiovascular responses to acute stress in chronically stressed rats and rats with myocardial infarcton

The present study was designed to determine the role of central vasopressin 1 receptors (V(1)R) in the regulation of cardiovascular parameters in chronically stressed infarcted rats and sham-operated rats under resting conditions and during exposure to acute alarming stress. The experiments were performed on four groups of conscious sham-operated and four groups of infarcted rats subjected to intraventricular infusion of either vehicle or a V(1)R antagonist (V(1)RANT). Two groups of infarcted and two groups of sham-operated rats were subjected to mild chronic stressing. Mean arterial blood pressure (MABP) and heart rate (HR) were determined under resting conditions and after exposure to acute stress (air jet). During vehicle infusion, MABP and HR increases in response to acute stress in the infarcted rats not subjected to chronic stress, and in the infarcted and sham-operated chronically stressed rats, were significantly greater than in the sham-operated rats not exposed to chronic stress. However, MABP and HR responses to acute stress in the chronically stressed infarcted rats and chronically stressed sham-operated rats did not differ. V(1)RANT abolished differences in cardiovascular responses to acute stress between the experimental groups. Resting cardiovascular parameters were not affected by any of the experimental treatments. It is concluded that chronic stressing enhances the pressor and tachycardic responses to acute stress in the sham-operated rats but does not further intensify these responses in infarcted rats.The results provide evidence that central V(1)Rs are involved in potentiation of cardiovascular responses to acute stress in chronically stressed rats, infarcted rats, and chronically stressed infarcted rats.

Blockade of angiotensin II AT1 receptors inhibits pressor action of centrally administered interleukin-1β in Sprague Dawley rats

The aim of the present study was to evaluate the influence of intraventricular administration of recombinant rat interleukin-1beta (IL-1beta) 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-1beta. 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 15 min under baseline conditions. This was followed by infusion of saline (0.9% sterile NaCl 5 microL/h) into the left cerebral ventricle (LCV). Measurements were continued during the next 60 min. 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-1beta (100 ng/h) and in series 3 with saline containing IL-1beta (100 ng/h) and angiotensin type 1 (AT1) receptors antagonist (Losartan, 10 microg/h). LCV infusion of saline alone did not influence MAP and HR while administration of IL-1beta elicited significant increase in MAP, but not in HR. The pressor effect was absent during combined infusion of IL-1beta and Losartan. Results of the study provide evidence that centrally administered IL-1beta exerts pressor effect, and reveal that this effect is mediated by stimulation of the brain angiotensin system and requires activation of AT1 receptors.

Interleukin-1 receptor antagonist reduces the magnitude of the pressor response to acute stress

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-1beta) 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.

Simvastatin Reduces Pressor Response to Centrally Administered Angiotensin II

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.

High-fat diet and chronic stress reduce central pressor and tachycardic effects of apelin in Sprague-Dawley rats.

Central application of apelin elevates blood pressure and influences neuroendocrine responses to stress and food consumption. However, it is not known whether the central cardiovascular effects of apelin depend also on caloric intake or chronic stress. The purpose of the present study was to determine the effects of intracerebroventricular administration of apelin on blood pressure (mean arterial blood pressure) and heart rate in conscious Sprague–Dawley rats consuming either a normal‐fat diet (NFD) or high‐fat diet (HFD) for 12 weeks. During the last 4 weeks of the food regime, the rats were exposed (NFDS and HFDS groups) or not exposed (NFDNS and HFDNS groups) to chronic stress. Each group was divided into two subgroups receiving intracerebroventricular infusions of either vehicle or apelin. Apelin elicited significant increase of mean arterial blood pressure and heart rate in the NFDNS rats. This effect was abolished in the HFDNS, HFDS and NFDS groups. HFD resulted in a significant elevation of blood concentrations of total cholesterol, triglycerides glucose and insulin. Chronic stress reduced plasma concentration of total and high‐density lipoprotein cholesterol, and increased plasma corticosterone concentration and APJ receptor mRNA expression in the hypothalamus, whereas a combination of a HFD with chronic stress resulted in the elevation of plasma triglycerides, total cholesterol and low‐density lipoprotein cholesterol, and in increased plasma corticosterone concentration, apelin concentration and APJ receptor mRNA expression in the hypothalamus. It is concluded that a HFD and chronic stress result in significant suppression of the central pressor action of apelin, and cause significant though not unidirectional changes of metabolic and endocrine parameters.

Oxytocin differently regulates pressor responses to stress in WKY and SHR rats: the role of central oxytocin and V1a receptors.

Abstract The role of central oxytocin in the regulation of cardiovascular parameters under resting conditions and during acute stress was investigated in male normotensive Wistar-Kyoto (WKY; n = 40) and spontaneously hypertensive rats (SHR; n = 28). In Experiment 1, mean arterial blood pressure (MABP) and heart rate (HR) were recorded in WKY and SHR rats at rest and after an air-jet stressor during intracerebroventricular (ICV) infusions of vehicle, oxytocin or oxytocin receptor (OTR) antagonist. In Experiment 2, the effects of vehicle, oxytocin and OTR antagonist were determined in WKY rats after prior administration of a V1a vasopressin receptor (V1aR) antagonist. Resting MABP and HR were not affected by any of the ICV infusions either in WKY or in SHR rats. In control experiments (vehicle), the pressor response to stress was significantly higher in SHR. Oxytocin enhanced the pressor response to stress in the WKY rats but reduced it in SHR. During V1aR blockade, oxytocin infusion entirely abolished the pressor response to stress in WKY rats. Combined blockade of V1aR and OTR elicited a significantly greater MABP response to stress than infusion of V1a antagonist and vehicle. This study reveals significant differences in the regulation of blood pressure in WKY and SHR rats during alarming stress. Specifically, the augmentation of the pressor response to stress by exogenous oxytocin in WKY rats is caused by its interaction with V1aR, and endogenous oxytocin regulates the magnitude of the pressor response to stress in WKY rats by simultaneous interaction with OTR and V1aR.