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.
Harding
J W
JW
Department of Veterinary and Comparative Anatomy, Washington State University, Pullman 99164.
Jensen
L L
LL
Quirk
W S
WS
Dewey
A L
AL
Wright
J W
JW
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