Evidence for sar1-ala8-angiotensin crossing the blood cerebrospinal fluid barrier to antagonize central effects of angiotensin II.
Injections of angiotensin II into the cerebral ventricles of the rat produces both a drinking and a pressor response. We have measured both responses simultaneously in conscious animals. The effect of saralasin acetate (P113), a specific angiotensin II competitive antagonist, has been studied on these angiotensin II induced responses. The results show that: (1) P113 given intravenously (i.v.) in doses of 500 ng/min or 1800 ng/min has no observable effect on 50 ng angiotensin given intraventricularly (IVT). At 72 mug/min, however, there was a 55% reduction in the drinking and pressor responses to 50 ng angiotensin II (IVT); (2) 500 ng of P113 given IVT abolished the effects of 50 ng angiotensin II also given IVT and (3) P113 given i.v. at all doses antagonized the pressor effects of angiotensin II (i.v.) responses. The data indicate that both the drinking and pressor responses to angiotensin II (IVT) injections are centrally mediated and show that when a high enough dose of P113 is given peripherally the central effects of angiotensin II can be reduced. This suggests that a fraction of the P113 injected i.v. may pass across the blood-CSF barrier. Since P113 has a similar structure to angiotensin II the results have implications for studies in which high peripheral doses of angiotensin II are used.
D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier; D004327:Drinking Behavior / Q000187:drug effects; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D051381:Rats; D012504:Saralasin / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D013268:Stimulation, Chemical
D000804:Angiotensin II; D012504:Saralasin