Stimulated mechanisms of Ca2+entry into vascular smooth muscle during NO synthesis inhibition in pregnant rats.

We have previously found that the vascular responsiveness to α1-adrenergic agonists is reduced in pregnant rats and enhanced in a rat model of pregnancy-induced hypertension produced by chronic treatment of pregnant rats with the nitric oxide (NO) synthase inhibitor N G-nitro-l-arginine methyl ester (l-NAME). The purpose of this study was to investigate whether the observed changes in vascular reactivity during normal pregnancy and during pregnancy-induced hypertension reflect changes in the mechanisms of Ca2+ entry into vascular smooth muscle.45Ca2+influx and active stress during α1-adrenergic stimulation by phenylephrine and membrane depolarization by 96 mM KCl were measured in deendothelialized aortic strips isolated from virgin and pregnant Sprague-Dawley rats untreated or treated with 1 mg/dayl-NAME for 4-6 days and incubated in Krebs solution containing increasing concentrations of extracellular Ca2+([Ca2+]e). In all groups of rats, both phenylephrine and 96 mM KCl caused [Ca2+]e-dependent increases in active stress and45Ca2+influx. The phenylephrine- and 96 mM KCl-induced active stress and Ca2+ influx were significantly reduced in pregnant rats but significantly enhanced in pregnant rats treated with l-NAME. The phenylephrine-induced Ca2+influx-stress relationship was significantly greater than that induced by 96 mM KCl in pregnant rats treated withl-NAME. The phenylephrine-induced Ca2+influx-stress relationship was reduced in pregnant rats but enhanced in pregnant rats treated withl-NAME. Chronic treatment withl-NAME had minimal effect on active stress, Ca2+ influx, and the Ca2+ influx-stress relationship in virgin rats. These results provide evidence that the mechanisms of Ca2+ entry into vascular smooth muscle are inhibited during pregnancy but enhanced during inhibition of NO synthesis in late pregnancy. The enhancement of the phenylephrine-induced Ca2+influx-stress relationship in pregnant rats treated withl-NAME suggests activation of other contractile mechanisms in addition to stimulation of Ca2+ entry. These mechanisms appear to be inhibited during normal pregnancy.