Endothelial vasodilatory function and blood pressure response to local and systemic hypercalcemia

Endothelial vasodilatory dysfunction occurs in primary hyperparathyroidism. Mechanistically it could be a sign of atherosclerosis, but improvement after parathyroidectomy suggests coupling to hypercalcemia and increased parathyroid hormone levels of patients.

A total of 12 volunteers underwent forearm venous occlusion plethysmography with systemic (intravenous) and local (brachial artery) infusion of calcium. Endothelium-dependent and endothelium-independent vasodilations were evaluated at stable hypercalcemia through infusion of methacholine and nitroprusside into the brachial artery, and an endothelial function index was calculated as the ratio between them.

Normal ionized blood calcium values rose 0.24 +/- 0.09 mmol/L in the cubital venous blood during local calcium infusion and 0.32 +/- 0.16 mmol/L during the systemic infusion. The systemic infusion raised systolic blood pressure (114 +/- 13 to 121 +/- 10 mm Hg; P < .05). It decreased the function index (1.28 +/- 0.40 to 1.00 +/- 0.14; P < .05; n = 11) due to an elevated endothelium-independent vasodilation (EIDV) (P < .05), despite the fact that serum parathyroid hormone values decreased (P< .01). A similar trend in vasodilatory responses was seen during local calcium infusion when the function index correlated inversely to the local blood calcium (r = -0.58, P < .05; n = 12).

Acute hypercalcemia results in dose-related impairment in endothelial vasodilatory function and increased systolic blood pressure. This substantiates the importance of hypercalcemia for cardiovascular complications and prospects for normalization by active treatment in primary hyperparathyroidism.