Evidence for distal tubular inhibition of calcium efflux by nisoldipine in the SHR rat.

Nisoldipine, a calcium channel blocking agent, is known to have antihypertensive, renal tubular and hemodynamic effects. The present studies were designed to examine the effects of this drug on the renal tubular transport of calcium in 12 saline-loaded SHR rats. Calcium-45 was infused into three different nephron segments: early proximal, late proximal and early distal sites with or without nisoldipine. Calcium efflux averaged 93.6 +/- 4.9 and 90.5 +/- 8.7% after early and late proximal administration, respectively, indicating that the proximal tubule and the loop of Henle are highly efficient in transporting calcium out of the tubule. In distal nephron segments, calcium transport was limited to 41.1 +/- 4.8% of the amount delivered to these tubules. Nisoldipine inhibited the efflux of simultaneously infused calcium. This apparent inhibitory effect occurred predominantly in distal nephron segments where the drug reduced calcium efflux from 41.1 +/- 4.8 to 22.5 +/- 2.7%, indicating a 45.3% reduction in net calcium reabsorption. The results are consistent with the interpretation that nisoldipine-induced reduction in the tubular efflux of calcium was secondary to a direct inhibition of voltage-sensitive, L-type calcium channels or to a blunting of the rate of phosphorylation of channel proteins by protein kinase C in the distal tubular epithelial cells.