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The Calcium Channel Blocker Diltiazem Lowers Serum Parathyroid Hormone Levels in Vivo and in Vitro^*

Endocrine-Hypertension Division, Departments of Medicine and Radiology, Brigham and Women's Hospital Boston, Massachusetts 02115

Address requests for reprints to: Ellen W. Seely, M.D., Endocrine-Hypertension Division, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, Massachusetts 02115.

PTH secretion is inversely related to the extracellular and cytosolic calcium (Ca²⁺) concentrations and, therefore, might be affected by calcium channel blockers such as diltiazem. To investigate the effects of diltiazem on parathyroid function in vivo, 15 subjects were treated with diltiazem (120–360 mg/day), and 15 subjects were treated with the nonspecific vasodilator hydralazine (75–150 mg/day). Diltiazem lowered serum PTH levels from 1.07 ± 0.07 to 0.87 ± 0.07 pg/L (P = 0.001), and increased urinary calcium and decreased urinary phosphate excretion (P < 0.001 and P < 0.01, respectively). The hydralazine-treated subjects had no significant differences in any of these parameters. To investigate this effect further, dispersed bovine parathyroid cells were incubated for 2 h with or without diltiazem. Regression analysis of PTH released vs. the concentration of diltiazem (10^–7–10^–4 mol/L) revealed a significant negative relationship (P < 0.01) with 40% inhibition of PTH release at 10^–4 mol/L (P < 0.01). The cytosolic Ca²⁺ concentration, measured using the Ca²⁺-sensitive fluorescent dye fura-2, was significantly increased in the presence of 10^–4 mol/L diltiazem (P < 0.01). In summary, diltiazem lowered PTH levels in vivo and in vitro, perhaps acting as a Ca²⁺ channel agonist in the parathyroid cell and inhibiting PTH release through a rise in the cytosolic Ca²⁺ concentration.

^* These results were presented in part at the American Society for Clinical Investigation, May 1–4, 1987, San Diego, CA, and the 41st Annual Fall Conference of the Council for High Blood Pressure Research, October 13–16, 1987, New Orleans, LA. This work was supported by NIH Grants HL-36001 and AM-36796), a Specialized Center of Research grant in Hypertension (HL-33697), and a grant from Marion Laboratories. The studies were performed at a Clinical Research Center supported by a grant from the Division of Research Resources (RR-2635), and the statistical analyses were performed in a CLINFO facility supported by the same grant.

Received August 31, 1988.