EVIDENCE FOR DISTAL TUBULAR INHIBITION OF CALCIUM EFFLUX BY NISOLDIPINE IN THE SHR RAT

Nisoldipine, a calcium channel blocking agent, is known to have antihy pertensive, renal tubular and hemodynamic effects. The present studies were designed to examine the effects of this drug on the renal tubula r transport of calcium in 12 saline-loaded SHR rats. Calcium-45 was in fused into three different nephron segments: early proximal, late prox imal and early distal sites with or without nisoldipine. Calcium efflu x averaged 93.6 +/- 4.9 and 90.5 +/- 8.7% after early and late proxima l administration, respectively, indicating that the proximal tubule an d the loop of Henle are highly efficient in transporting calcium out o f the tubule. In distal nephron segments, calcium transport was limite d to 41.1 +/- 4.8% of the amount delivered to these tubules. Nisoldipi ne inhibited the efflux of simultaneously infused calcium. This appare nt 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 res ults are consistent with the interpretation that nisoldipine-induced r eduction in the tubular efflux of calcium was secondary to a direct in hibition of voltage-sensitive, L-type calcium channels or to a bluntin g of the rate of phosphorylation of channel proteins by protein kinase C in the distal tubular epithelial cells.