Gender-specific inhibition of Ca2+ entry mechanisms of arterial vasoconstriction by sex hormones

1. The clinical observation that hypertension is more common in males and p ostmenopausal women than in premenopausal women suggests vascular protectiv e effects of female sex hormones, including hormone-mediated inhibition of tone, The purpose of the present study was to investigate whether the Ca2mobilization mechanisms of vascular smooth muscle contraction are modified by gender and sex hormones, 2. Active stress and [Ca-45(2+)] influx were measured in deendothelialized aortic strips isolated from intact and gonadectomized male and female Sprag ue-Dawley rats, In normal Krebs' (2.5 mmol/L Ca2+), both phenylephrine (Phe ; 10(-5) mol/L) and membrane depolarization by 96 mmol/L KCI increased acti ve stress to 15.5 +/- 1.3 x 10(3) and 14.5 +/- 1.2 x 10(3) N/m(2), respecti vely, and Ca2+ influx to 28.4+/-1.4 and 32.3+/-1.5 mu mol/kg per min, respe ctively in intact males, The Phe- and KCl-induced stress and Ca2+ influx we re significantly reduced in intact females, Gonadectomy was associated with no significant changes in the Phe- and KCl-induced stress and Ca2+ influx in males, but was associated with significant enhancement in females. In Ca 2+-free (2 mmol/L EGTA) Krebs', stimulation of intracellular Ca2+ release b y Phe or caffeine (25-mmol/L) caused a transient contraction that was not s ignificantly different in all groups of rats. 3. Exogenous application of 17 beta-oestradiol, progesterone or testosteron e to aortic strips caused concentration-dependent inhibition of Phe- and KC l-stimulated contractions and Ca2+ influx, 17 beta-Oestradiol was the most effective hormone and its relative potency was intact males, castrated male s and ovariectomized females > intact females. 4. Thus, vascular reactivity and Ca2+ entry in aortic smooth muscle are red uced in the presence and enhanced in the absence of female gonads, Both mal e and female sex hormones cause vascular relaxation, mainly by inhibiting C a2+ entry, with oestrogen being the most effective, particularly in the, ab sence of female gonads. The results suggest that a cellular mechanism of oe strogen-induced vascular relaxation involving inhibition of Ca2+ entry into vascular smooth muscle is gender dependent.