Verapamil improves defective duodenal calcium absorption in experimental chronic renal failure

Experiments were carried out to establish whether abnormalities in cellular calcium metabolism in chronic renal failure contributed to the impaired production of 1,25-dihydroxy vitamin D3 [1,25(OH)2D3]. For this purpose the calcium influx blocker verapamil was administered chronically to 5/6 nephrectomized rats (SNX) and sham-operated rats (sham). SNX and sham-nontreated animals served as controls. Fractional duodenal calcium absorption was severely depressed in SNX rats, compared to sham group. Administration of verapamil to SNX rats caused an improvement in calcium absorption despite similar degrees of renal insufficiency as in the nontreated SNX animals. The effect of verapamil requires residual renal parenchyma, since it was not reproduced in bilaterally nephrectomized rats. 45Ca uptake by renal cortical slices obtained from SNX rats was significantly elevated, as compared to sham group, and was corrected in uremic rats treated with verapamil. Plasma concentrations of 25-hydroxy vitamin D3 (25-OH-D3) were similar in all experimental groups. The 1,25(OH)2D3 plasma level in SNX rats was similar to values obtained in the control group, with an almost 2-fold increase in verapamil-treated animals. Quin-2 measurements of cytoplasmic calcium concentration in cultured proximal tubular cells revealed that verapamil prevents calcium bursts provoked by anoxic insult, by parathyroid hormone and by alpha 1-adrenergic stimuli. We conclude that verapamil treatment of SNX rats improves the duodenal absorption of calcium via augmentation of 1,25(OH)2D3 production.(ABSTRACT TRUNCATED AT 250 WORDS)