MECHANISMS OF THE ANTIHYPERTENSIVE EFFECTS OF DIETARY CALCIUM AND ROLE OF CALCITONIN-GENE-RELATED PEPTIDE IN HYPERTENSION

Alterations in calcium metabolism and calcium-regulating hormones have been described in essential hypertension. However, the mechanisms tha t mediate these responses are unknown. In previous studies, using the genetically spontaneously hypertensive rat and the mineralocorticoid-s alt (DOG-salt) hypertensive rat model, we and others have observed tha t oral calcium supplementation attenuates the associated increase in p eripheral vascular resistance and consequently lowers blood pressure ( BP). When hypertensive patients (n = 8, diastolic BP 90-95 mmHg (1 mmH g = 133.3 Pa)) were given daily oral calcium supplementation (1.4 g el emental calcium), both systolic and diastolic BP were decreased (5-10 mmHg, p < 0.01). The only biochemical variables significantly changed were serum ionized calcium and intact parathyroid hormone (PTH, 1-84) (p < 0.05); furthermore, the levels of calcitonin gene related peptide (CGRP), measured by both radioimmunoassay and radioreceptor assay, sh owed a marked 75% increase (p < 0.001). The antihypertensive effects o f Ca2+ and the increased levels of CGRP in the circulation returned to baseline levels immediately following cessation of calcium supplement ation, suggesting that the effects of calcium on BP and CGRP are speci fic. On the basis of these observations we propose that the antihypert ensive effect of dietary calcium supplementation, at least in part, is mediated through CGRP.