Differential sensitisation to central cardiovascular effects of angiotensin II in rats with a myocardial infarct: Relevance to stress and interaction with vasopressin

Abstract

The purpose of the present study was to elucidate if rats with myocardial infarction manifest altered responsiveness to central cardiovascular effects of low doses of angiotensin II (ANG II), and if ANG II and vasopressin (VP) cooperate in the central regulation of cardiovascular functions at rest and during stress. Conscious Sprague-Dawley rats with myocardial infarction induced by left coronary artery ligation, or sham-ligated (SL) controls were infused intracerebroventricularly with artificial cerebrospinal fluid (aCSF), ANG II, ANG II + VP or ANG II + V1a receptor antagonist (V1ANT) 4 weeks after cardiac surgery. In the infarcted but not in the SL rats, the resting mean arterial blood pressure (MABP) was significantly elevated by infusions of ANG II and ANG II + VP, while infusion of ANG II + V1ANT was not effective. During administration of aCSF, the pressor, and tachycardic responses to an air-jet stressor were significantly greater in the infarcted than in the SL rats. In the SL rats, the pressor responses to the stressor were significantly greater during infusions of ANG II, ANG II + VP and ANG II + V1ANT than during infusion of aCSF. The tachycardic response in the SL rats was enhanced only by the combined infusion of ANG II + VP. In the infarcted rats, the pressor and the tachycardic responses to the stressor were similar in all groups. It is concluded that: (1) under resting conditions the infarcted rats manifest sensitisation to the central pressor effect of ANG II and that this effect depends on concomitant stimulation of V1a VP receptors, (2) central ANG II may enhance the pressor response to an alarming stressor in the SL rats through an action which does not depend on the concomitant stimulation of V1a receptors, (3) the cooperative action of ANG II and VP is required for intensification of the tachycardic response to the alarming stressor in the SL rats and (4) exaggeration of the cardiovascular responses to the alarming stressor in the infarcted rats cannot be further augmented by an additional stimulation of central ANG II receptors or combined stimulation of ANG II and VP receptors.

Angiotensin Converting Enzyme Inhibition Reduces Cardiovascular Responses to Acute Stress in Myocardially Infarcted and Chronically Stressed Rats

“…In previous studies, it was demonstrated that this effect significantly depends on the activation of the brain renin-angiotensin system as it could be abolished by ICV administration of AT1 receptor blockers and potentiated by central administration of Ang II [17–19]. The present study shows that significant attenuation of exaggerated cardiovascular responses to acute stress may be achieved both in infarcted and in chronically stressed rats by oral administration of captopril.…”

“…We have also found that vasopressin and stimulation of V1 receptors participate in Ang II-induced potentiation of the cardiovascular responses to acute stress in infarcted rats [18, 19]. Thus, reduction of the cardiovascular responses to acute stress by captopril could result from its inhibitory effect on generation of Ang II in vasopressin secreting neurons.…”

“…With regard to the regulation of blood pressure, Saiki et al [14] reported that the blockade of AT1 receptors in the brain by intracerebroventricular (ICV) administration of losartan or saralasin reduces the cardiovascular responses to immobilization stress, whereas De Matteo et al [15] and Mayorov and Head [16] have found that the blockade of AT1 receptors in the rostral ventrolateral medulla (RVLM) and dorsomedial hypothalamus with candesartan or losartan reduces significantly the pressor response to 7-minute exposure to air jet stressor in rabbits. Furthermore, the studies of Zhang et al [17] and Cudnoch-Jedrzejewska et al [18, 19] revealed that the blockade of AT1 receptors with losartan abolishes elevation of cardiovascular responses to stress in rats with myocardial infarction.…”

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

“…Similarly, oxytocin produced opposite effects to vasopressin (Dobruch et al 2005;Cudnoch-Jędrzejewska et al 2008;Stojicić et al 2008). For instance, blockade of oxytocin receptors enhanced the pressor and tachycardic responses to stress in the sham-operated rats while being ineffective in the infarcted rats, whereas blockade of V1 receptors with d(CH 2 ) 5 Tyr(Me) 2 ,Ala-NH 2 9 ]AVP was not effective in the sham-operated rats but it markedly strengthened the pressor and tachycardic responses to stress during the post-infarct state (Dobruch et al 2005;Cudnoch-Jędrzejewska et al 2007).…”

“…The rate of ICV infusion of oxytocin used in the present study (100 ng/h) may be considered to be relatively low in comparison to the doses administered by other authors. Oxytocin was infused at this rate in order to match the rate of vasopressin infusion that has been used in our previous investigations (Dobruch et al 2005;Cudnoch-Jędrzejewska et al 2008). Therefore, it cannot be excluded that a higher dose of oxytocin would affect function of the cardiovascular system under baseline conditions.…”