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

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Abstract
To assess changes in responsiveness to pressor agents in experimental hypertension, pressor dose-response curves to graded doses of angiotensin II (AII) and norepinephrine (NE) were examined in anesthetized normal rats and rats with early (< 6 wk) or chronic (> 4 mo.) 2-kidney 1 clip renovascular hypertension and deoxycorticosterone (DOC) salt hypertension. Occupancy of receptors by endogenous AII was reduced by converting enzyme inhibition with captopril or bilateral nephrectomy. Rats with DOC-salts hypertension were significantly more responsive to AII than normal rats or rats with renovascular hypertension (P < 0.05). Captopril administration had no effect on AII 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 AII dose-response curves after captopril. Bilateral nephrectomy also eliminated the differences between the responsiveness of DOC-salt and other groups, although responsivenss after bilateral nephrectomy was lower than that after captopril. Captopril administration to nephrectomized animals had no effect on responsiveness. Receptor occupancy by endogenous AII is the major factor that alters pressor responsiveness to AII in normal and experimental hypertensive rats. Duration of hypertension seemed to play no role. Norepinephrine responsiveness was not significantly different between the experimental groups. 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 renin-angiotensin system therefore appears important in modulating pressor responses to norepinephrine in the intact animal, and this interaction differs from the effect demonstrated in isolated tissues.