Vascular effects of progesterone - Role of cellular calcium regulation

Vascular actions of progesterone have been reported, independently of estro gen, affecting both blood pressure and other aspects of the cardiovascular system. To study possible mechanisms underlying these effects, we examined the effects of P in vivo in intact rats and in vitro in isolated artery and vascular smooth muscle cell preparations. In anesthetized Sprague-Dawley r ats, bolus intravenous injections of P (100 mug/kg) significantly decreased presser responses to norepinephrine (0.3 mug/kg). In vitro, progesterone ( 10(-8) to 10(-5) mmol/L) produced a significant, dose-dependent relaxation of isolated helical strips, both of rat tail artery precontracted with KCl (60 mmol/L) or arginine vasopressin (3 nmol/L), and of rat aorta precontrac ted with KCl (60 mmol/L) or norepinephrine (0.1 mu mol/L). In isolated vasc ular smooth muscle cells, progesterone (5 x 10(-7) mol/L) reversibly inhibi ted KCl (30 mmol/L) -induced elevation of cytosolic-free calcium by 64.1+/- 5.5% (P<0.05), and in whole-cell patch-clamp experiments, progesterone (5x1 0(-6) mol/L) reversibly and significantly blunted L-type calcium channel in ward current, decreasing peak inward current to 65.7+/-4.3% of the control value (P<0.05). Our results provide evidence that progesterone is a vasoact ive hormone, inhibiting agonist-induced vasoconstriction. The data further suggest that progesterone effects on vascular tissue may, at least in part, be mediated by modulation of the L-type calcium channel current activity a nd, consequently, of cytosolic-free calcium content.