Area postrema is critical for angiotensin-induced hypertension in rats.

Abstract

SUMMARYThe effect of surgical ablation of the area postrema on acute (5-10 minutes) and chronic (5-10 days) increases in mean arterial pressure produced by intravenous infusion of angiotensin II hi conscious, instrumented rats was studied. In agreement with previous studies, pressor responses of area postrema-ablated rats (a = 11) to acute angiotensin II infusion were identical to those of control sham-lesioned rats (n = 13). In these same rats, however, a 5-day infusion of angiotensin II produced a sustained hypertension hi the sham-lesioned group whereas mean arterial pressure was increased only transiently (1-3 days) hi the area postrema-ablated rats. No differences before infusion of arterial pressure, heart rate, water intake, urinary sodium excretion, and urinary potassium excretion were observed between sham-lesioned and area postrema-ablated rats; only arterial pressure was changed significantly during angiotensin II infusion hi either group. Twenty-four hours after terminating angiotensin II infusion, mean arterial pressure was within the normotensive range hi both shamlesioned and area postrema-ablated rats. In a separate group of sham-lesioned (n = 13) and area postrema-ablated (n = 12) rats, angiotensin n was infused intravenously for a 10-day period; mean arterial pressure was increased significantly over the entire 10-day infusion hi sham-lesioned rats, but for only 1 day hi area postrema-ablated rats. An intact area postrema appears necessary for the development of chronic, but not acute, hypertension during intravenous infusion of angiotensin II hi the rat. Supported by National Heart, Lung, and Blood Institute Grants HL24111 andHL32981.Address for reprints: Dr. Gregory D. Fink, Dept. of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824.Received January 27, 1986; accepted October 20, 1986. perimental hypertension. A detailed analysis 1 of many of these studies led to the conclusion that ANG II does not cause chronic hypertension by direct vascular constriction, but rather by an ability to stimulate a more slowly developing (hours to days) pressor mechanism: a mechanism whose sensitivity to ANG II increases with prolonged exposure to the hormone. Actions of ANG II on aldosterone secretion, 2 renal handling of salt and water,

Purinergic receptors in the brainstem mediate hypotension and bradycardia.

“…31 Furthermore, the injection of the adenosine receptor agonists NECA and PIA has recently been shown to exert substantial depressor effects in some medullary sites, including the NTS and the area postrema. 32 The fact that adenosine has such potent hypotensive actions in the area postrema is especially interesting, since this area is essential in the development of hypertension in twokidney, one clip rats 33 and caffeine, an adenosine receptor antagonist, has been shown to enhance the pressor effect of angiotensin II in this model of hypertension. Our studies demonstrate that adenosine and ATP both reduce blood pressure and heart rate when injected into the NTS and the area postrema.…”

Sex differences in angiotensin II- induced hypertension

“…It has been reported that chronic low-dose ANG II-induced hypertension, which develops over a period of days, is not due to the peripheral vasoconstrictor activity of ANG II, but is most likely the result of excitation of the sympathetic nerve activity (8,17). Recent studies from our laboratory have shown in mice that decreases in blood pressure induced by ganglionic blockade are much smaller on day 1 as compared to day 7 of ANG II infusion, thus suggesting that an enhancement of sympathetic outflow contributes to the ANG II-induced progressive increase in blood pressure (21).…”

“…Angiotensin II (ANG II) is an important factor in many forms of clinical and experimental hypertension. In animals, low doses of ANG II are known to induce neurogenic hypertension via the central nervous system by acting through brain circumventricular organs (8,9). An increasing body of evidence has shown that the central and peripheral effects of www.bjournal.com.br ANG II involve activation of reactive oxygen (10,11).…”

Sex differences in angiotensin II- induced hypertension

“…Central actions of ANG II increase sympathetic nerve activity and modulate reflex regulation of heart rate through actions of the peptide on sensory circumventricular organs (15) such as the area postrema, subfornical organ and organum vasculosum of the lamina terminalis (8,(16)(17)(18)(19)(20). It has been reported that chronic low-dose ANG II-induced hypertension, which develops over a period of days, is not due to the peripheral vasoconstrictor activity of ANG II, but is most likely the result of excitation of the sympathetic nerve activity (8,17).…”