Responsiveness to pressor agents in experimental renovascular and steroid hypertension. Effects of converting enzyme inhibitor and nephrectomy.

To assess changes in responsireness to pressor agents in experimental hypertension, we examined pressor dose-response curves to graded doses of angiotensin II (All) and norepinephrine (NE) in anesthetized normal rats and rats with eariy (< 6 weeks) or chronic (> 4 months) two-kidney one clip renovascular hypertension and deoxycorticosterone (DOC) salt hypertension. Occupancy of receptors by endogenous AH was reduced by converting enzyme inhibition with captopril or bilateral nephrectomy. Rats with DOC-salt hypertension were significantly more responsive to AH than normal rats or rats with renovascular hypertension (p < 0.05). Captopril administration had no effect upon AH responsiveness in DOC-salt hypertension, but enhanced the responses of normal rats and rats with renovascular hypertension, so that there were no significant differences in the All dose-response curves after captopril. Bilateral nephrectomy also eliminated the differences between the responsiveness of DOC-salt and other groups, although responsiveness after bilateral nephrectomy was lower than that after captopril. Captopril administration to nephrectomized animals had no effect upon responsiveness. It is concluded that receptor occupancy by endogenous AH is the major factor that alters pressor responsiveness to AH in normal and experimental hypertensive rats. Duration of hypertension seemed to play no role. By contrast, norepinephrine responsiveness was not significantly different between the experimental groups. However, captopril treatment increased the slope of the dose response curves in intact but not nephrectomized groups. This increased sensitivity appears to be due to inhibition of the renin-angiotensin system, since it was also produced by saralasin infusion, but not by bradykinin infusion. The reninangiotensin system therefore appears to be important in modulating pressor responses to norepinephrine in the intact animal, and this interaction differs from the effect that has been demonstrated in isolated tissues. (Hypertension 4: 238-244, 1982)