Effects of long-acting angiotensin-converting enzyme inhibitor, imidapril, on the lower limit of cerebral blood flow autoregulation in hypertensive rats

Abstract

The objective of the present study was to examine the effects of a long-acting angiotensin converting enzyme inhibitor, imidapril ((4S)-1-methyl-3-¿(2S)-2-[N-(1S)-1-ethoxycarbonyl-3-phenylpropyl) amino] propionyl¿-2-oxoimidazolidine-4-carboxylic acid hydrochloride), for 7 days on the cerebral blood flow autoregulatory response to hypotension in hypertensive rats. We measured the cerebral blood flow at rest and during hemorrhagic hypotension, using laser-Doppler flowmetry. At the same time, the absolute baseline cerebral blood flow values in the parietal cortex were quantified with the hydrogen clearance method. After administration of imidapril at a dose of 5 mg/kg/day for 7 days, the resting value of mean arterial blood pressure was significantly decreased by 25 mm Hg (P < 0.001), cerebral vascular resistance was lowered by 14.4% (P < 0.05) and the lower limit of cerebral blood flow autoregulation was shifted to a lower level, 106+/-11 mm Hg (mean +/- S.D.), from 137+/-8 mm Hg in the control group (P < 0.001), while resting cerebral blood flow remained unchanged. The present results demonstrated that imidapril preserves cerebral blood flow and significantly shifts the lower limit of cerebral autoregulation towards lower blood pressure levels.