Pregnancy enhances endothelium-dependent relaxation of ovine uterine artery: role of NO and intracellular Ca(2+).
The present study tested the hypothesis that the pregnancy-associated increase in endothelium-dependent relaxation of the uterine artery was mediated primarily by an increase in nitric oxide (NO) release, resulting in a reduction in smooth muscle intracellular Ca(2+) concentration ([Ca(2+)](i)). Uterine arteries obtained from nonpregnant and near-term (140 days gestation) pregnant sheep were used. The Ca(2+) ionophore A23187 induced endothelium-dependent relaxations in both nonpregnant and pregnant uterine arteries, with an increased relaxation in the pregnant tissue. In contrast, endothelium-independent relaxations induced by sodium nitroprusside were the same in nonpregnant and pregnant arteries. In addition, removal of the endothelium significantly increased noradrenaline-induced contractions in pregnant, but not nonpregnant, uterine arteries. In accordance, pregnancy increased both basal and A23187-stimulated NO releases in the uterine artery. Simultaneous measurement of tension and [Ca(2+)](i) in the smooth muscle demonstrated a linear correlation with the slope of unity between A23187-induced relaxation and the reduction of [Ca(2+)](i) in both nonpregnant and pregnant uterine arteries. The A23187-induced reduction of [Ca(2+)](i) was significantly enhanced in pregnant, compared with nonpregnant, uterine arteries. The results indicate that pregnancy increases NO release, which, through decreasing [Ca(2+)](i) in the smooth muscle, accounts for the increased endothelium-dependent relaxation of the uterine artery. Signal transduction pathways distal to NO production are not changed by pregnancy.
Xiao
D
D
Center for Perinatal Biology, Department of Pharmacology and Physiology, Loma Linda University School of Medicine, Loma Linda, California 92350, USA.
Pearce
W J
WJ
Zhang
L
L
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D007476:Ionophores / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D012016:Reference Values; D012756:Sheep; D014599:Uterus / Q000098:blood supply*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D007476:Ionophores; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D000001:Calcimycin; D002118:Calcium; D009638:Norepinephrine