Abnormal Renin Short Feedback Loop in Essential Hypertension Is Reversible with Converting Enzyme Inhibition

The suppression of renin release by angiotensin II (AII) (the so-called short feedback loop) is blunted in essential hypertension. To determine whether this abnormality is reversible, renin release was assessed in sodium-restricted essential hypertensives and normal controls: (a) during the administration of captopril for varying intervals and (b) following the infusion of graded doses of AII (0.3-3 ng/kg per min) before and after plasma levels of AII had been chronically reduced with captopril (25-50 mg every 6 h) for 70 h.

In control subjects, the maximal increment above control in plasma renin activity (PRA) after a single dose of captopril (11.9±3 ng/ml per h) was significantly (P < 0.02) greater than in hypertensives (8.1±1.7 ng/ml per h) despite similar reductions in AII levels and significantly greater decrements in diastolic blood pressure in the hypertensives. When captopril was continued for 70 h, the PRA increments above base line in hypertensive subjects (11.4±2.9 ng/ml per h) rose to levels seen in the controls (11±2.6 ng/ml per h); there were no significant differences in the AII or diastolic blood pressure decrements between the two groups.

Compared with normotensive subjects, AII failed to suppress renin release in hypertensive subjects despite significantly greater diastolic blood increments and comparable AII levels achieved at each AII dose.

After captopril treatment, AII now produced significant declines in PRA in the hypertensives; moreover, comparing declines pre- and postcaptopril, greater PRA decrements were seen either at comparable rises in levels of AII or diastolic blood pressure. Finally, the suppression of PRA by AII postcaptopril in hypertensives was now indistinguishable from that seen in normal controls. Thus, the impaired regulation of renin by AII is reversible with prolonged captopril treatment, suggesting that this abnormality is not due to a fixed structural defect but to a reversible lesion.

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