CARDIOVASCULAR DEVELOPMENT AFTER ENALAPRIL IN SPONTANEOUSLY HYPERTENSIVE AND WISTAR-KYOTO RATS

We studied the long-term effects after withdrawal of enalapril, an ang iotensin-converting enzyme inhibitor, on tail systolic pressure and ca rdiovascular structural properties in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Observations in control rats were f rom 4 to 35 weeks of age, whereas treated rats received enalapril from 4 to 20 weeks and were studied for a further 15 weeks. We measured bl ood pressure and the ratio of left ventricle weight to body weight and derived methoxamine log dose-perfusion pressure curves in the isolate d hindquarter bed. From the changes in resistance properties we also e stimated the changes in structure using a model developed previously. During therapy, blood pressure was depressed to a common value in both strains. After drug withdrawal, by age 35 weeks, previously treated S HR developed only mild hypertension, whereas blood pressure of WKY had recovered to the corresponding control level. At 21 weeks, soon after enalapril was stopped, left ventricular development was depressed in both strains; the depression was slightly greater in SHR, but that of vascular resistance was proportionately similar in each strain. Late c ardiovascular development between 21 and 35 weeks was attenuated in th e previously treated groups. For the left ventricle, it was similar in each strain, but for the vasculature, late development was relatively smaller in SHR than WKY. In the former, the pattern of development be tween 21 and 35 weeks was the same as in untreated controls and appear ed to be mediated in response to the rise in blood pressure. In previo usly treated WKY, the rise in blood pressure was smaller, so that thei r relatively greater late vascular development was largely through ano ther mechanism, probably involving a direct action on smooth muscle gr owth, through a product of the converting enzyme. This non-blood press ure-dependent component of late development was absent in previously t reated SHR. We conclude that the products of angiotensin-converting en zyme play an important role in the normal development of each strain. The between-strain differences in late development contribute to the r elatively greater restoration of blood pressure in previously treated WKY compared with SHR and for the mildness of the hypertension in the latter. In normal cardiovascular development, the action of converting enzyme is relatively nonspecific, suggesting that it does not play ot her than a general role in the pathogenesis of hypertension.