title: Hypoxia impairs endothelium-dependent relaxation in organ cultured pulmonary artery.
abstract: In intrapulmonary arteries cultured under hypoxic conditions (5% oxygen) for 7 days, endothelium-dependent relaxation and cGMP accumulation induced by substance P were decreased as compared to those of a normoxic control (20% oxygen). In rabbit mesenteric arteries exposed to chronic hypoxia, however, endothelial dysfunction was not observed. Furthermore, in endothelium-denuded pulmonary arteries exposed to hypoxia, neither relaxation nor cGMP accumulation due to sodium nitroprusside differed from those of the normoxic control. Hypoxia did not change the mRNA expression of endothelial NO synthase (eNOS), the protein expression of eNOS or the eNOS regulatory protein caveolin-1 as assessed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) or whole-mount immunostaining. Morphological study revealed atrophy of endothelial cells and condensation of the eNOS protein in many cells. These results suggest that chronic hypoxia impaired NO-mediated arterial relaxation without changing either the eNOS protein expression or the NO-sensitivity of smooth muscle cells in pulmonary arteries. Changes in cell structure and organization may be involved in endothelial dysfunction.
authors.affiliation: Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Yayoi 1-1-1, Tokyo 113-8657, Bunkyo, Japan. murata@jvm2.vm.a.u-tokyo.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Murata
authors.forename: H
authors.initials: H
authors.lastname: Yamawaki
authors.forename: M
authors.initials: M
authors.lastname: Hori
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: H
authors.initials: H
authors.lastname: Ozaki
authors.forename: H
authors.initials: H
authors.lastname: Karaki
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001708:Biopterins / Q000031:analogs & derivatives* / Q000494:pharmacology; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D000860:Hypoxia / Q000503:physiopathology*; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D009599:Nitroprusside / Q000494:pharmacology; D009924:Organ Culture Techniques; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D013373:Substance P / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D051242:Caveolin 1; D022461:Caveolins; D012333:RNA, Messenger; D014665:Vasodilator Agents; D009599:Nitroprusside; D001708:Biopterins; D013373:Substance P; D015759:Ionomycin; D001120:Arginine; D015237:Dinoprost; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; C003402:sapropterin; D006152:Cyclic GMP