Cardiovascular and Renal Actions of Calcium Channel Blocker Chemical Subgroups: a Search for Renal Specificity

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Abstract
The diuretic and natriuretic responses to structurally distinct classes of Ca2+ channel blockers have been compared, to determine whether any agent provoked K+-sparing natriuresis, and to assess the relation of such responses with drug effects on blood pressure. Conscious normotensive Sprague-Dawley rats received vehicle or one of the following drugs in an oral saline load (40 mL kg−1): nifedipine, nimodipine, nitrendipine, prenylamine, cinnarizine, flunarizine, diltiazem, verapamil, hydrochlorothiazide, amiloride, or hydralazine, at doses from 0.316 to 100 mg kg−1. Urine was collected for 6 h. Blood pressure was monitored directly in parallel studies. Diltiazem (31.6, 100 mg kg−1) and flunarizine (100 mg kg−1) enhanced urine and electrolyte excretion in spite of marked hypotension; diltiazem was the only drug to produce dose-related renal responses. In contrast, equihypotensive doses of hydralazine and nifedipine produced overt urine and electrolyte retention. Nitrendipine and prenylamine (0.316 mg kg−1 each) produced slight diuresis or natriuresis without altering blood pressure; higher doses had no effect. The 31.6 mg kg−1 doses of verapamil, nitrendipine, and nimodipine markedly reduced blood pressure, but neither enhanced nor limited urine and electrolyte excretion. Cinnarizine failed to produce any cardiovascular or renal effects. Diuretic responses evoked by the Ca2+ channel blockers were not class-specific, showed no tendency towards sparing K+, were generally weaker than those produced by low doses of amiloride or hydrochlorothiazide, and were dissociable from drug-induced changes in blood pressure.