Acute sympathoexcitatory action of angiotensin II in conscious baroreceptor-denervated rats

Abstract

Xu, Ling, and Alan F. Sved. Acute sympathoexcitatory action of angiotensin II in conscious baroreceptor-denervated rats. Am J Physiol Regulatory Integrative Comp Physiol 283: R451-R459, 2002. First published April 18, 2002 10.1152/ ajpregu.00648.2001.-Angiotensin II (ANG II) has complex actions on the cardiovascular system. ANG II may act to increase sympathetic vasomotor outflow, but acutely the sympathoexcitatory actions of exogenous ANG II may be opposed by ANG II-induced increases in arterial pressure (AP), evoking baroreceptor-mediated decreases in sympathetic nerve activity (SNA). To examine this hypothesis, the effect of ANG II infusion on lumbar SNA was measured in unanesthetized chronic sinoaortic-denervated rats. Chronic sinoaortic-denervated rats had no reflex heart rate (HR) responses to pharmacologically evoked increases or decreases in AP. Similarly, in these denervated rats, nitroprusside-induced hypotension had no effect on lumbar SNA; however, phenylephrine-induced increases in AP were still associated with transient decreases in SNA. In control rats, infusion of ANG II (100 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 iv) increased AP and decreased HR and SNA. In contrast, ANG II infusion increased lumbar SNA and HR in sinoaortic-denervated rats. In rats that underwent sinoaortic denervation surgery but still had residual baroreceptor reflex-evoked changes in HR, the effect of ANG II on HR and SNA was variable and correlated to the extent of baroreceptor reflex impairment. The present data suggest that pressor concentrations of ANG II in rats act rapidly to increase lumbar SNA and HR, although baroreceptor reflexes normally mask these effects of ANG II. Furthermore, these studies highlight the importance of fully characterizing sinoaortic-denervated rats used in experiments examining the role of baroreceptor reflexes. sympathetic nervous system; arterial blood pressure; hypertension; renin ANGIOTENSIN II (ANG II) has complex actions on the cardiovascular system. Acutely, increases in circulating levels of ANG II produced by infusion of exogenous ANG II increase arterial pressure (AP) by acting directly to constrict vascular smooth muscle. However, accumulating evidence indicates that a chronically elevated circulating level of ANG II increases AP via an increase in sympathetic vasomotor tone (5, 6, 10, 39). For example, ganglionic blockade produces a greater depressor response during long-term infusion of ANG II than that observed during acute ANG II infusions in control animals (8,23,26,52). Furthermore, doses of ANG II that do not increase AP during acute infusion (i.e., subpressor doses) do result in a delayed increase in AP that can be totally reversed with sympatholytic drugs (14, 36). Indeed, increases in sympathetic nerve activity (SNA) have been recorded in animals infused chronically with ANG II (29). These studies collectively suggest that chronically elevated levels of ANG II in the circulation may stimulate sympathetic outflow (5, 6).Although ANG II at acutely subpressor doses seems to elicit a delayed sym...

Vagal afferent input alters the discharge of osmotic and ANG II-responsive median preoptic neurons projecting to the hypothalamic paraventricular nucleus

“…For example, several investigators have postulated that the pressor action of exogenously administered ANG II masks the ability of ANG II to stimulate thirst, vasopressin secretion, and sympathetic outflow. In this regard, barodenervation or prevention of the ANG II-evoked increase in ABP does enhance thirst and acutely increases sympathetic outflow (Robinson and Evered, 1987;Schreihofer et al, 2000;Stocker et al, 2001Stocker et al, , 2002Xu and Sved, 2002;Stocker et al, 2004). To the extent it has been examined, similar observations have been reported during increases in plasma osmolality (Weiss et al, 1996;Chen and Toney, 2001;Stocker et al, 2001Stocker et al, , 2002.…”

Adenoviral inhibition of AT1a receptors in the paraventricular nucleus inhibits acute increases in mean arterial blood pressure in the rat

“…Further importance of these pathways is demonstrated by the impact of sinoaortic deafferentation on the pressor response induced by ANG II. After baroreceptor denervation, ANG II increased lumbar sympathetic nerve activity and HR (43).…”

“…Bolus injections (13), short-term infusions (9,28,43), and long-term infusions (17,24,27,28), as well as the effects, of endogenous ANG II (37,38,39) have been shown to be at least partially mediated by an activation of the sympathetic nervous system through a stimulation of the brain. In the present studies, a short-term infusion of ANG II was chosen to study the role of PVN AT 1 Rs to initially investigate the effectiveness of the shRNA.…”

“…Acute administration of ANG II increases blood pressure, largely by constricting vascular smooth muscle and increasing peripheral resistance. In addition, circulating ANG II increases blood pressure through neurogenically mediated mechanisms during acute and long-term ANG II exposure (9,22,28,33,43).In order for ANG II to stimulate neurally mediated increases in blood pressure, ANG II must act at angiotensin type 1 (AT 1 ) receptors (AT 1 Rs) in regions of the brain that recognize changes in circulating hormones, since ANG II does not cross the blood-brain barrier. However, circulating ANG II stimulates AT 1 Rs (10) in specific regions of the brain that are devoid of a blood-brain barrier, such as the subfornical organ (SFO) (20), organum vasculosum of the lamina terminalis (OVLT) (14), and area postrema (18).…”

“…Acute administration of ANG II increases blood pressure, largely by constricting vascular smooth muscle and increasing peripheral resistance. In addition, circulating ANG II increases blood pressure through neurogenically mediated mechanisms during acute and long-term ANG II exposure (9,22,28,33,43).…”