RENAL TUBULAR EFFECTS OF CALCIUM-ANTAGONISTS

Calcium channel blockers have diuretic and natriuretic properties in normal animals and humans. The renal mechanism by which this natriuresis is produced has not yet been completely defined although dihydropyridine derivatives evoke it in experimental animals independently of any effects on renal blood flow or on the glomerular filtration rate. Injections or infusions into the renal artery indicate that the renal excretory effect is secondary to a direct action on renal tubular water and solute reabsorption but not to renal hemodynamic changes. Studies undertaken to localize the site of action of dihydropyridine calcium antagonists on renal tubules by renal clearance and micropuncture techniques suggest that both proximal and distal tubular sites are involved. Primary sites of action in distal convoluted tubules and in the collecting duct have been identified for felodipine and nisoldipine during sodium infusion, whereas sites for nitrendipine in proximal tubules have been demonstrated in strict hydropenia. Both changes in the tubuloglomerular feedback setting and suppression of aldosterone secretion have been proposed to explain some of these effects. The changes do not, however, seem to be dependent on renal innervation. In normal humans, the degree and duration of natriuresis and diuresis correlate with the dose of dihydropyridine derivatives and the extent of systemic pressure reduction. Clearance studies of normal subjects indicate an effect of different dihydropyridine derivatives on tubular fluid and electrolyte reabsorption. Nicardipine and nifedipine are reported to exert proximal tubular actions based either on urate and phosphate excretion or water and lithium clearance. The measurement of tubular indices following felodipine administration suggests a proximal tubular site of action. Dihydropyridine derivatives possess diuretic and natriuretic properties due to their direct effect on net renal tubular sodium and water reabsorption. The exact site of this action and the mechanisms involved have not yet been fully elaborated.