Leakage of angiotensin converting enzyme inhibitors from the cerebral ventricles into the peripheral circulation in conscious, spontaneously hypertensive rats.
The inhibitory effects of SQ14225 and MK421 injected into the lateral brain ventricle (i.c.v.) and intravenously (i.v.) on pressor responses to intravenous (i.v.) angiotensin I(AI, 400 ng/kg i.v.) were compared in conscious spontaneously hypertensive rats (SHR). Both the i.c.v. and i.v. inhibitors suppressed the increase in blood pressure produced by intravenous injections of AI in a dose dependent manner. The inhibition of pressor responses to i.v. AI were rapid in onset and decayed with time following i.v. captopril and MK421, while the effects of i.c.v. inhibitors were slower in onset and were maintained for a longer time. The activity of MK421, either i.v. or i.c.v. persisted for longer compared to that of SQ14225 in conscious SHR. It was concluded that SQ14225 and MK421 readily leaked from the brain ventricles to the peripheral circulation and this observation suggested that the central hypotensive effects of these inhibitors might be partly attributed to peripheral blockade of angiotensin I conversion in conscious SHR.
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001812:Blood-Brain Barrier; D002216:Captopril / Q000008:administration & dosage / Q000378:metabolism; D002552:Cerebral Ventricles / Q000378:metabolism*; D004151:Dipeptides / Q000008:administration & dosage / Q000378:metabolism; D004656:Enalapril; D006973:Hypertension / Q000097:blood / Q000378:metabolism*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D051381:Rats; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D004656:Enalapril; D002216:Captopril