Hypercalcemia induced by acute norepinephrine infusion is not mediated by PTH nor PTHrP secretion in man

Abstract

Parathyroid hormone (PTH), when acutely infused, exerts potent cardiovascular action in man, such as: hypotension and positive chronotropic and inotropic effects. Parathyroid hormone-related protein (PTHrP) also induces hypotension and positive inotropic and chronotropic effect in the rat, and an influence of the adrenergic system on PTH and PTHrP secretion has been postulated. Therefore, the aim of the present study was to evaluate the effect of an acute norepinephrine (NE) infusion on blood pressure (BP), heart rate (HR), serum total (tCa) and ionized calcium (+ + Ca), cyclic 3′-5′ AMP (cAMP), immunoreactive intact [1–84] PTH and PTHrP levels in 5 healthy normotensive subjects, before and after a pretreatment with a beta-blocking agent, pindolol. NE, when acutely infused for 10 min, induced a significant increase in systolic and diastolic BP from the 10th to the 20th min, with a parallel significant decrease in HR, a significant increase in serum tCa and + + Ca and cAMP, with a parallel significant decrease in intact iPTH levels. Serum iPTHrP, during NE infusion, did not change from the baseline values. During pindolol, NE infusion did not induce any significant change in systolic and diastolic BP, in serum tCa and + + Ca, cAMP, intact iPTH and iPTHrP levels. Our results suggest that NE induces acute hypercalcemia which is not mediated by PTH nor PTHrP secretion. Hypercalcemic effect of NE seems to be mediated by adrenergic system, since it is abolished by a beta-blocking agent. Conversely, the significant decrease of serum intact iPTH is probably due to the hypercalcemic effect of NE. However, the involvement of other systems in the action of NE, like prostaglandin or RAA system, cannot be excluded.