Effects of central and peripheral angiotensin blockade in hypertensive rats.
The angiotensin II (AII) antagonist [Sar1-Ala8]AII (Saralasin) was injected into the brain ventricles (IVT) and intravenously (IV) in five different types of hypertensive unanesthetized rats. Renal hypertension was studied 16-22 days after kidney clipping. Intravenous infusions of cumulative doses (0.1-100 microgram/kg per min) and IVT injections (5-40 microgram) of Saralasin did not change mean arterial pressure (MAP) in controls and in one-clip, one-kidney Goldblatt hypertension, whereas MAP decreased in one-clip, two-kidney Goldblatt hypertension following IV and IVT Saralasin. In two-clip, two kidney hypertensive rats, IVT Saralasin decreased MAP but was ineffective when infused IV. Both IV and IVT Saralasin increased MAP in DOC hypertension. In spontaneously hypertensive (SH) rats, IV Saralasin increased MAP; IVT injection decreased MAP. The effect of IVT Saralasin in SH rats persisted 15-20 h after nephrectomy. We conclude that plasma AII may contribute to peripheral and central mechanisms of blood pressure regulation. The dissociation of the effects of IV and IVT Saralasin and the persistance of blood pressure decrease in nephrectomized SH rats following IVT Saralasin further support a role for locally formed brain angiotensin.
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000097:blood / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003900:Desoxycorticosterone; D005260:Female; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology*; D006977:Hypertension, Renal / Q000503:physiopathology; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D012083:Renin / Q000097:blood; D012504:Saralasin / Q000494:pharmacology
D000804:Angiotensin II; D003900:Desoxycorticosterone; D012083:Renin; D012504:Saralasin