HYPERPARATHYROIDISM, PLATELET INTRACELLULAR FREE CALCIUM AND HYPERTENSION IN CHRONIC-RENAL-FAILURE

To investigate possible relationships between hyperparathyroidism, alterations in intracellular free calcium concentration ([Ca2+]i) and hypertension in chronic renal failure, serum concentrations of intact parathyroid hormone (PTH) were measured by two-site immunometric assay, and platelet ([Ca2+]i) was assessed using the fluorescent indicator fura-2. Thirty-six patients with chronic renal failure were studied, 10 with normal serum PTH concentrations (mean 8.0 +/- 0.6 pmol/liter), 17 with elevated serum PTH (35.0 +/- 7.2 pmol/liter) and 9 patients with elevated PTH (36.2 +/- 5.9 pmol/liter) who were receiving nifedipine. Platelet [Ca2+]i was increased in patients with elevated PTH, compared with those in whom PTH was normal (138 +/- 16 vs. 83 +/- 7 nmol/liter, P < 0.01). A linear relation was observed between serum PTH and platelet [Ca2+]i in these patients (r = 0.818, P < 0.001). In contrast, platelet [Ca2+]i was not elevated (84 +/- 9 nmol/liter) in the patients with elevated PTH who were receiving nifedipine. A linear relation was also present between both serum PTH (r = 0.616, P < 0.001) and platelet [Ca2+]i (r = 0.576, P < 0.005) and mean blood pressure. Nine patients with hyperparathyroidism were restudied after treatment with the vitamin D analogue alfacalcidol. This resulted in significant decreases in serum PTH (P < 0.01), platelet [Ca2+]i (P < 0.02), and mean blood pressure (P < 0.05). These studies indicate that [Ca2+]i may be increased early in renal failure, and that this increase occurs in association with both hyperparathyroidism and hypertension. Furthermore, treatment of hyperparathyroidism with alfacalcidol may result in reductions in both [Ca2+]i and blood pressure. The lack of elevation in [Ca2+]i in nifedipine-treated patients with hyperpamthyroidism suggests that, in uremia, increases in cytosolic calcium induced by PTH or other factors may be mediated in part by dihydropyridine-sensitive mechanisms.