Central angiotensin II receptors mediate hemodynamic response variability to stressors

Abstract

We examined whether ANG II receptors in the central nervous system mediate hemodynamic responses to pharmacological (cocaine) and behavioral (cold water) stressors. After administration of cocaine (5 mg/kg iv), rats were classified as vascular responders (VR) if their pressor response was due entirely to an increase in systemic vascular resistance (SVR) despite a decrease in cardiac output (CO). Cocaine elicited a pressor response in mixed responders (MR) that was dependent on small increases in both SVR and CO. ANG II (30 ng/5 microl icv, 5 min before cocaine) augmented the decrease in CO in VR and prevented the increase in CO in MR. Administration of [Sar(1),Thr(8)]ANG II (20 microg/5 microl icv; sarthran) before cocaine attenuated the decrease in CO and the large increase in SVR in VR so that they were no longer different from MR. Losartan (20 microg icv) or captopril (50 microg icv) preceding cocaine administration also attenuated the decrease in CO and the large increase in SVR seen in VR only. The role of angiotensin was not specific for cocaine, because ANG II (icv) pretreatment before startle with cold water (1 cm deep) enhanced the decrease in CO and the increase in SVR in both MR and VR, whereas losartan (icv) pretreatment before startle attenuated the decrease in CO and the increase in SVR in VR so that they were no longer different from MR. These data suggest that central ANG II receptors mediate the greater vascular and cardiac responsiveness in vascular responders to acute pharmacological and behavioral stressors.

Angiotensin II and CRF receptors in the central nucleus of the amygdala mediate hemodynamic response variability to cocaine in conscious rats

“…Therefore, we conclude that activation of AT 1 receptors in the CeA is necessary for the greater vascular response observed in vascular responders. This is consistent with previous observations demonstrating that intracerebroventricular administration of Ang receptor antagonists or converting enzyme inhibitors attenuated vasoconstrictor responses to cocaine or cold stress in vascular responders selectively whereas administration of Ang enhanced these responses (Knuepfer et al, 2005; Rowe et al, 2006). These data suggest that Ang signaling in the CeA may differ between vascular and mixed responders resulting in varying responses to cocaine in different populations.…”

“…Ang receptors in the CNS play an important role in autonomic and neurohumoral responses to behavioral and pharmacological stress (Jezova et al, 1998; Knuepfer et al, 2005; Rowe et al, 2006; Saiki et al, 1997). Ang and AT 1 receptors exist in the amygdala and, in particular, in the CeA (Brownfield et al, 1982; von Bohlen und Halbach and Albrecht, 1998).…”

“…Recently, we found that intracerebroventricular administration of Ang or CRF receptor antagonists reduced the greater increase in systemic vascular resistance observed in vascular responders during behavioral stress or cocaine administration (Knuepfer et al, 2005; Rowe et al, 2006). However, intracerebroventricular administration of a drug affects broad areas of the brain.…”

The angiotensin-converting enzyme inhibitor perindopril treatment alters cardiovascular and subjective effects of methamphetamine in humans

“…Relatively few previous reports have examined the effects of ACE inhibitors on increases in blood pressure produced by methamphetamine or other psychostimulants. Cocaine-induced increases in blood pressure in animals were recently shown to be mediated by central AT-1 receptors, with this effect attenuated by pretreatment with an ACE inhibitor (Rowe et al, 2006). The mechanisms through which perindopril increased methamphetamine-induced blood pressure in the present study are unknown, but appear to involve different effects of ACE inhibition on blood pressure under basal conditions and after treatment with methamphetamine.…”

Angiotensin and NMDA receptors in the median preoptic nucleus mediate hemodynamic response patterns to stress

“…We reported that ANG II receptor antagonists or a converting enzyme inhibitor administered intracerebroventricularly prevented the greater increase in systemic vascular resistance in vascular responders in response to cocaine or to startle with cold water (40). In contrast, intracerebroventricular administration of ANG II enhanced the increase in systemic vascular resistance (40). These data suggest that AT 1 receptors in the central nervous system (CNS) mediate and may be responsible for response variability although the site of action was not clear.…”