(Hypertension. 2001;37:142.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
Vascular Effects of Progesterone
Role of Cellular Calcium Regulation
From the Institute of Internal Medicine and Geriatrics (M.B., L.J.D., G.L.), University of Palermo, Palermo, Italy; the Department of Physiology (J.S., E.K., P.K.T.P.), University of Alberta, Canada; and the Hypertension Center (L.M.R.), NY-Presbyterian Hospital/Cornell University Medical Center, New York, NY.
Correspondence to Lawrence M. Resnick, Hypertension Center, New York Presbyterian Hospital/Cornell University Medical Center, 525 E. 68th St, Starr 4 Pavilion, New York, NY 10021. E-mail lmr2004{at}med.cornell.edu
Abstract—Vascular actions of progesterone have been reported, independently of estrogen, 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 rats, bolus intravenous injections of P (100 µg/kg) significantly decreased pressor responses to norepinephrine (0.3 µg/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 precontracted with KCl (60 mmol/L) or norepinephrine (0.1 µmol/L). In isolated vascular smooth muscle cells, progesterone (5x10-7 mol/L) reversibly inhibited 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 (5x10-6 mol/L) reversibly and significantly blunted L-type calcium channel inward 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 vasoactive 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 and, consequently, of cytosolic-free calcium content.
Key Words: progesterone • intracellular calcium • vascular smooth muscle • sex steroid hormones • L-type calcium channel • hypertension • menopause
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