Direct effects of nicotine on contractility of the uterine artery in pregnancy.
Recent studies indicate that smoking/nicotine increases maternal blood pressure and decrease in uterine blood flow in pregnancy. However, the mechanisms are not fully understood. The present study was designed to test the hypothesis that nicotine exposure decreases endothelium-dependent relaxation and increases vascular contractility of the uterine artery in pregnancy. Uterine arteries were isolated from near-term ( approximately 140 days gestation) pregnant ewes. Arteries were subjected to acute (20 min) or chronic (48 h) nicotine treatment, and agonist-induced contractions and relaxations were measured in tissue bath. Endothelial eNOS was detected by immunohistochemistry in situ in arteries and by Western blotting in isolated endothelial cells. Chronic nicotine treatment produced a concentration-dependent increase in alpha(1)-adrenoceptor agonist phenylephrine-induced contractions. In contrast, the acute treatment showed no effect. Inhibition of eNOS with N(G)-nitro-L-arginine (L-NNA) significantly increased phenylephrine-induced contractions, which was abolished in uterine arteries after chronic nicotine treatment. In the presence of L-NNA, there was no significant difference in phenylephrine-induced contractions between control and nicotine-treated vessels. Chronic, but not acute, nicotine treatment significantly attenuated the calcium ionophore A23187-induced relaxations. Unlike A23187, the endothelium-independent relaxation mediated by sodium nitroprusside was not affected by nicotine. Endothelial eNOS protein levels and the phosphorylation levels of eNOS(Ser1179) were significantly decreased in nicotine-treated uterine arteries. The results suggest that nicotine impairs uterine vascular function in pregnancy, which may lead to an increased vascular resistance and a decrease in uterine blood flow.
Xiao
Daliao
D
Center for Perinatal Biology, Department of Pharmacology and Physiology, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA. dxiao@llu.edu
Huang
Xiaohui
X
Yang
Shumei
S
Zhang
Lubo
L
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D009538:Nicotine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000032:analysis; D019335:Nitroarginine / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D012756:Sheep; D014599:Uterus / Q000098:blood supply*; D014661:Vasoconstriction / Q000187:drug effects*
D018340:Receptors, Adrenergic, alpha-1; D019335:Nitroarginine; D009569:Nitric Oxide; D009538:Nicotine; D052250:Nitric Oxide Synthase Type III