Opposite effects of enalapril and nitrendipine on natriuretic response to atrial natriuretic factor. Renal function evaluated with clearance studies in humans

In clearance studies, we analyzed the effect of Ca²⁺ entry blockade with nitrendipine treatment (20 mg b.i.d. for 4 days) and of converting enzyme inhibition with enalapril treatment (20 mg b.i.d. for 4 days) on renal response to atrial natriuretic factor (ANF) (25 μg bolus followed by an infusion of 0.03 μg/kg/min for 90 minutes) in six healthy volunteers who were taking 300 mmol sodium daily. In a control study ANF was administered without Ca²⁺ entry blockade or converting enzyme inhibition. Natriuresis rose from 239 ± 38 to 605 ± 137 μmol/min in the control study (p < 0.05), from 330 ± 53 to 943 ± 152 μmol/min with Ca²⁺ entry blockade (p < 0.05), and from 236 ± 22 to 344 ± 39 μmol/min with converting enzyme inhibition (NS). ANF induced a rise in maximal free water clearance, inulin clearance, and in the excretion of multiple electrocytes except potassium. Fractional lithium reabsorption fell. In general, these effects were stronger during Ca²⁺ entry blockade and blunted during converting enzyme inhibition. p-Aminohippurate clearance tended to decrease during the control study (NS), remained constant during Ca²⁺ entry blockade, and decreased significantly when ANF was infused during converting enzyme inhibition (p < 0.05 vs. control and vs. Ca²⁺ entry blockade study). Blood pressure was lowered by Ca²⁺ entry blockade and, to a somewhat greater extent, by converting enzyme inhibition, but ANF administration induced no additional fall except for a short-term drop during Ca²⁺ entry blockade. From these data we conclude that, in healthy humans, the effects of ANF on natriuresis and renal sodium handling are enhanced by Ca²⁺ entry blockade and blunted by converting enzyme inhibition. These effects might be explained by amplification of (preglomerular?) ANF-induced vasodilation during Ca²⁺ entry blockade and amplification of (postglomerular?) ANF-induced vasoconstriction during converting enzyme inhibition.