Hypotensive action of parathyroid hormone in hypoparathyroid and hyperparathyroid rats.

Abstract

SUMMARY Experimental and clinical data suggest an association between chronic hyperparathyroidism and hypertension, but acute infusion of parathyroid hormone causes vasodilation and hypotension. These observations imply that chronic and acute parathyroid states affect blood pressure through different mechanism(s), either by modification of vascular receptors or by an ionophoretic effect of parathyroid hormone. The effect of parathyroid status induced by dietary calcium manipulations or by surgical ablation of the parathyroid gland on the hypotensive response of parathyroid hormone infusion was studied in rats. At 4 weeks of age 24 male rats were divided into four equal groups. Three groups were sham-operated, and one group was thyroparathyroidectomized. Only the thyroparathyroidectomized group was treated with thyroxine, 10 /xg/kg/day. The control and thyroparathyroidectomized groups were raised on a 1.4% calcium diet; the other two groups were raised on 0.005% and 2.8% calcium diets. After 8 weeks on the diets, parathyroid hormone was infused through a venous cannula at 5 and 10 ng/kg doses and blood pressure was measured through arterial cannulas. The results indicate that hyperparathyroidism and hypocalcemia induced by the low calcium diet attenuated the hypotensive response to parathyroid hormone compared with responses in rats raised on a 1.4% calcium diet. In hypoparathyroid rats (2.8% Ca diet) with hypercalcemia, the hypotensive response was also reduced. However, in hypoparathyroid (thyroparathyroidectomized) rats with hypocalcemia, the hypotensive response was enhanced. The data suggest that chronic parathyroid status, as well as hypercalcemia, alters the hypotensive response to parathyroid hormone infusion, presumably by altering the vascular parathyroid hormone receptors or by some other mechanism. (Hypertension 11: 509-513, 1988 Yet hyperparathyroidism is often associated with increased BP in humans 6 " 8 and rats. 9 "" The cellular basis for chronic PTH action on BP regulation is unknown.12 " 14 PTH may influence the sympathetic nervous system and vasoactive hormones either directly or indirectly through changes in plasma ionic cal- cium. 15 ' l6 The accentuation of hypertension by hyperparathyroidism or long-term PTH administration, blunted vascular reactivity in the hypercalcemic state, 17 and hypocalcemia after parathyroidectomy are all consistent with the hypothesis that PTH exerts an ionophoretic and, therefore, a permissive effect on the vasoconstrictive and hypertensive action of extracellular fluid calcium.18 " 20 The purpose of the present study was to investigate the effect of long-term modifications of PTH status by surgical and dietary means in normotensive Sprague-Dawley rats on the hypotensive response to acute PTH administration. In addition, the plasma and bone calcemic parameters were measured to document the alterations in systemic calcium metabolism and PTH status.

Dietary calcium and blood pressure in experimental models of hypertension. A review.

“…Nevertheless, reductions in dietary calcium comparable to those used to modify central nervous system calcium levels are reported to alter central nervous system norepinephrine levels. Baksi 122 reported that 8 weeks of a 0.005% calcium diet reduced hypothalamic norepinephrine and dopamine content in Sprague-Dawley rats. Restricted dietary calcium has also been reported to alter peripheral catecholamine levels.…”

Hypocalcemic cardiac failure in the Emergency Department

“…Increased levels of parathyroid hormone are known to activate protein kinase C in cardiac myocytes, leading to hypertrophic growth of the myocardium and exerting an inotropic influence (27,28). In animal models of hypoparathyroidism, infusion of parathyroid hormone causes a hypotensive response by a largely unknown mechanism (29). This patient's calcitonin level was inexplicably elevated and not felt to be the cause of his hypocalcemia.…”

Effects of Voluntary Exercise on Bone Growth and Calcium Metabolism in Spontaneously Hypertensive Rats

“…Schleiffer et al (18) demonstrated that parathyroidectomy of the SHR restricted the blood pressure elevation. Baski (2) reported that while acute PTH infusion in normal rats caused hypotention, chronic PTH infusion caused hypertension contrariwise. This result suggests that the PTH alone is one of the factors that induce the increase in the cell free calcium ion.…”