Cardiovascular Development After Enalapril in Spontaneously Hypertensive and Wistar-Kyoto Rats

Abstract

Abstract We studied the long-term effects after withdrawal of enalapril, an angiotensin-converting enzyme inhibitor, on tail systolic pressure and cardiovascular structural properties in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Observations in control rats were from 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 blood pressure and the ratio of left ventricle weight to body weight and derived methoxamine log dose–perfusion pressure curves in the isolated hindquarter bed. From the changes in resistance properties we also estimated 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 SHR 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 cardiovascular development between 21 and 35 weeks was attenuated in the 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 between 21 and 35 weeks was the same as in untreated controls and appeared to be mediated in response to the rise in blood pressure. In previously treated WKY, the rise in blood pressure was smaller, so that their relatively greater late vascular development was largely through another mechanism, probably involving a direct action on smooth muscle growth, through a product of the converting enzyme. This non–blood pressure–dependent component of late development was absent in previously treated SHR. We conclude that the products of angiotensin-converting enzyme play an important role in the normal development of each strain. The between-strain differences in late development contribute to the relatively 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 other than a general role in the pathogenesis of hypertension.