Prolonged converting enzyme inhibition in non-modulating hypertension

Abstract

Patients with normal- or high-renin non-modulating essential hypertension fail to shift their adrenal sensitivity on a low sodium diet in response to an infusion of angiotensin II (Ang II). In a prior study, 72 hours of converting enzyme inhibition (CEI) partially corrected this subnormal aldosterone response to Ang II in patients with non-modulating hypertension. Since it was uncertain whether the failure to restore normal adrenal responsiveness reflected a continued abnormality or an insufficient duration of CEI, the present study was performed wherein subjects were studied before CEI and then 72 hours and 6 weeks after CEI. Adrenal and renovascular responses were assessed in 13 subjects with normal- or high-renin hypertension in response to an infusion of Ang II (0.3, 1.0, and 3.0 ng/kg/min) in balance on a 10 meq Na+/100 meq K+ diet. Eight of 13 had a normal plasma aldosterone increment above control levels (≥15 ng/dl) and were classified as modulators; the remaining subjects (five of 13) were classified as non-modulators. Enalapril was then administered for 72 hours and 6 weeks, and the assessment of the Ang II dose-response relations was repeated. In the modulators, there was no change compared with levels before CEI in the aldosterone dose-response curve or threshold sensitivity to infused Ang II at either 3 days or 6 weeks after CEI administration. In the non-modulators, CEI for 72 hours partially restored aldosterone responsiveness, but more prolonged CEI for 6 weeks completely corrected the defect, restoring aldosterone responsiveness on a sodium-restricted diet to that seen in modulators and in normotensive control subjects. The threshold dose for a significant increase in plasma aldosterone above control levels progressively shifted from 3 ng/kg/min (72 hours of CEI) to 1 ng/kg/min (6 weeks of CEI). After CEI, basal p-aminohippurate clearance progressively increased in both groups, but a significant increment above control levels was only observed in non-modulators at 6 weeks; CEI enhanced renovascular responsiveness to infused Ang II equally in the two hypertensive subgroups. Complete correction of the renal abnormality in a previous study and the adrenal defect in the present study by CEI without demonstrable changes in circulating Ang II levels provide support for a tissue defect in the renin-angiotensin system in non-modulating hypertensive subjects. © 1989 American Heart Association, Inc.