Upregulation of eNOS in pregnant ovine uterine arteries by chronic hypoxia.
We tested the hypothesis that chronic high-altitude (3,820 m) hypoxia during pregnancy was associated with the upregulation of endothelial nitric oxide (NO) synthase (eNOS) protein and mRNA in ovine uterine artery endothelium and enhanced endothelium-dependent relaxation. In pregnant sheep, norepinephrine-induced dose-dependent contractions were increased by removal of the endothelium in both control and hypoxic uterine arteries. The increment was significantly higher in hypoxic tissues. The calcium ionophore A23187-induced relaxation of the uterine artery was significantly enhanced in hypoxic compared with control tissues. However, sodium nitroprusside- and 8-bromoguanosine 3',5'-cyclic monophosphate-induced relaxations were not changed. Accordingly, chronic hypoxia significantly increased basal and A23187-induced NO release. Chronic hypoxia increased eNOS protein and mRNA levels in the endothelium from uterine but not femoral or renal arteries. In nonpregnant animals, chronic hypoxia increased eNOS mRNA in uterine artery endothelium but had no effects on eNOS protein, NO release, or endothelium-dependent relaxation. Chronic hypoxia selectively augments pregnancy-associated upregulation of eNOS gene expression and endothelium-dependent relaxation of the uterine artery.
Xiao
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Center for Perinatal Biology, Department of Pharmacology and Physiology, Loma Linda University School of Medicine, Loma Linda, California 92350, USA.
Bird
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Magness
R R
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Longo
L D
LD
Zhang
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D000532:Altitude Sickness / Q000378:metabolism; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002908:Chronic Disease; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000201:enzymology; D005260:Female; D005263:Femoral Artery / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D000860:Hypoxia / Q000378:metabolism*; D007476:Ionophores / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D012077:Renal Artery / Q000201:enzymology; D012756:Sheep; D014469:Umbilical Arteries / Q000201:enzymology; D014599:Uterus / Q000098:blood supply* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D007476:Ionophores; D012333:RNA, Messenger; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D000001:Calcimycin; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP; D009638:Norepinephrine