Cerebroventricular infusion of angiotensin antagonist does not influence hypertensive response to blood-borne angiotensin II.
Blood-borne angiotensin II (AII) has several actions that result from interaction of the peptide with known AII-sensitive brain sites (i.e. circumventricular organs). In the rat, electrolytic ablation of the organum vasculosum of the lamina terminalis and surrounding periventricular hypothalamus, a known AII-sensitive area, will prevent development of hypertension in response to chronic intravenous AII infusion. The purpose of the present study was to determine if selective pharmacological blockade of brain AII receptors, rather than electrolytic lesion, would block chronic intravenous (i.v.) AII-induced hypertension. Male Sprague-Dawley rats were instrumented with chronic indwelling arterial and venous catheters and a lateral cerebroventricular cannula. In initial experiments, 5-day intracerebroventricular (i.c.v.) infusion of 1Sar,8Thr-AII (sarthran) at a dose of 1 microgram/h was found to produce functional blockade of central AII receptors with minimal effects on peripheral receptors (assessed by measuring the pressor responses to acute i.c.v. and i.v. AII administration). This dose of sarthran also had no agonistic effects in rats maintained on high sodium intake. Continuous blockade of brain AII receptors with i.c.v. sarthran had no effect on the ultimate development of hypertension seen in response to 5-day i.v. AII infusion (10 or 20 ng/min) coupled with high sodium intake. The failure of i.c.v. sarthran infusion to block chronic i.v. AII-induced hypertension probably reflects the inability of i.c.v. sarthran to gain access to a critical brain site(s) at which i.v. AII acts to cause increased arterial pressure.
D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D004347:Drug Interactions; D006973:Hypertension / Q000139:chemically induced*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D009490:Neurosecretory Systems / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000494:pharmacology
D000804:Angiotensin II; C014805:angiotensin II, Sar(1)-Thr(8)-; D012964:Sodium