Brain angiotensin: critical role in the ongoing regulation of body fluid homeostasis and cardiovascular function.
The existence of an endogenous brain-angiotensin system and its association with cardiovascular and body water regulation has been recognized for over a decade. Nevertheless, the importance of the brain-angiotensin system to the instantaneous regulation of these processes has not been firmly established. A 5-minute intracerebroventricular (ICV) infusion of the angiotensin antagonist, [Sar1,Thr8]-AII, effectively lowered the blood pressure in normotensive rats. Additionally, application of the selective aminopeptidase inhibitor, bestatin, given alone, resulted in a dramatic increase in blood pressure and a robust drinking response. Both effects were 100% blockable by [Sar1,Thr8]-AII pretreatment. Predictably, an aminopeptidase inhibitor, bestatin, greatly elongated the half-lives of AII and AIII in the cerebroventricles. Since neither of these treatments included the introduction of exogenous angiotensins, we have concluded that perturbations of the endogenous brain-angiotensin system are effective at rapidly influencing both cardiovascular and body fluid homeostasis, thus highlighting the paramount role played by brain angiotensin in their ongoing regulation.
Department of Veterinary and Comparative Anatomy, Washington State University, Pullman 99164.
J W
JW
Harding
L L
LL
Jensen
W S
WS
Quirk
A L
AL
Dewey
J W
JW
Wright
D000626:Aminopeptidases / Q000037:antagonists & inhibitors; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000809:Angiotensins / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000502:physiology*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D004326:Drinking; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D014882:Water-Electrolyte Balance / Q000187:drug effects
D000809:Angiotensins; D000804:Angiotensin II; C014805:angiotensin II, Sar(1)-Thr(8)-; D000626:Aminopeptidases; D007930:Leucine; C012211:ubenimex