Verapamil induces PTH resistance but increases duodenal calcium absorption in rats

In vitro, verapamil inhibits duodenal Ca absorption, parathyroid hormone (PTH) secretion, and PTH-stimulated bone resorption. This study was designed to determine if any effects of chronic oral verapamil treatment on PTH secretion-action are reflected by changes in vitamin D metabolism, duodenal Ca absorption, and bone Ca content. Rats (100 g) received verapamil in the drinking water at doses of 4, 20, or 100 mumol.kg-1.day-1 for 2 wk. Verapamil administration did not significantly affect growth, plasma Ca or phosphate, or bone Ca content. However, verapamil treatment was associated with a dose-dependent 90% increase in plasma PTH levels. The elevated PTH was accompanied by a 22% decrease in 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels, such that there was a significant negative correlation (r = -0.52; P less than 0.01) between PTH and 1,25(OH)2D3 levels. Despite the decreased plasma 1,25(OH)2D3 levels, verapamil treatment was associated with a dose-dependent increase in duodenal Ca absorption. The increased Ca absorption did not seem to be caused by a verapamil-induced increased intestinal sensitivity to 1,25(OH)2D3, since verapamil-treated vitamin D-deficient rats showed the same absorptive response to administered 1,25(OH)2D3 as untreated rats. Thus chronic oral verapamil treatment induces an apparent PTH resistance but does not appear to have major effects on overall Ca homeostasis in young male rats.