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 hi 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 (215 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 sodiumrestricted diet to that seen hi modulators and in normotensive control subjects. The threshold dose for a significant increase hi 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 hi 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. (Hypertension 1989;13:371-377)

Impaired Sodium Excretion During Mental Stress in Mild Essential Hypertension

“…Recently, we have demonstrated that hypertensive subjects display an enhanced antinatriuresis in response to exogenously administered Ang II, 20 confirming the hyperresponsiveness to Ang II, which has been described for the renal vasculature 10,21,22 and for cardiac structure. 23 In contrast to Light et al, 5 we did not find a difference in stress-induced natriuresis between normotensive subjects with and those without a family history of hypertension.…”

Hypertension and the kidney: culprit and victim

“…As a result, renal vasodilation is impaired, and aldosterone inappropriately elevated. Angiotensin converting enzyme inhibitors normalized both disturbances [23], stressing the central role of the reninangiotensin system in the link between renal vasoconstriction and impaired sodium excretion. Almost a decade ago, Sealey et al proposed nephron heterogeneity, that is existence of a subpopulation of ischaemic nephrons which is responsible for elevated intrarenal angiotensin II levels, as basis for impaired sodium excretion and hypertension [24].…”

Angiotensin-Converting Enzyme Inhibitors

“…A “nonmodulator” subgroup of salt‐sensitive individuals has been described in whom a high‐salt diet increases BP but does not cause normal renal vasodilation or suppression of aldosterone release. Chronic ACE inhibition corrects this defect 25 but the relative roles of genes, environment, and other influences in the non‐modulator phenotype is the subject of ongoing investigation.…”