Oral verapamil and calcium and vitamin D metabolism in rats: effect of dietary calcium.
Prior studies showed that chronic oral verapamil administration increased plasma immunoreactive parathyroid hormone (irPTH) but decreased 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels in rats fed a high (1.2%)-Ca diet. These and other findings suggested that verapamil may induce target-organ PTH resistance. This study determined the effects of verapamil (4, 20, or 100 mumol.kg-1.day-1 for 2 wk) in rats fed high (1.2%)-, low-normal (0.47%)-, and low (0.02%)-Ca diets (higher irPTH levels). With 1.2 and 0.47% Ca diets, verapamil administration was associated with increases in irPTH (92 and 44%, respectively) and decreases in 1,25(OH)2D3 levels (22 and 21%, respectively), increases in duodenal Ca transport (13 and 8%, respectively), and increases in tibia mineral content (1.3 and 2.8%, respectively). The decrease in 1,25(OH)2D3 levels was caused by decreased production, not by increased clearance. In contrast, verapamil was without effect in rats fed the 0.02% Ca diet. Thus severe dietary Ca deficiency abolished the stimulatory effects of verapamil on irPTH levels, Ca absorption, and tibia mineral content. Importantly, these results indicate that verapamil, in contrast to nifedipine, appears not to have adverse effects on Ca homeostasis in rats, irrespective of dietary Ca intake.
Fox
J
J
Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Della-Santina
C P
CP
D000284:Administration, Oral; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D002117:Calcitriol / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002136:Calcium, Dietary / Q000494:pharmacology*; D004386:Duodenum / Q000378:metabolism; D006706:Homeostasis; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D013977:Tibia / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology*; D014807:Vitamin D / Q000378:metabolism*
D002136:Calcium, Dietary; D010281:Parathyroid Hormone; D014807:Vitamin D; D014700:Verapamil; D002117:Calcitriol; D002118:Calcium