title: Hypoxia-inducible factor 1 alpha contributes to pulmonary vascular dysfunction in lung ischemia-reperfusion injury.
abstract: The revascularization therapy of pulmonary embolism is associated with ischemia-reperfusion (IR) injury. However, the effect of IR injury on pulmonary arterial endothelial function has not been elucidated. Male Sprague-Dawley rats were divided into a control, an IR and an IR plus hypoxia-inducible factor 1 alpha (HIF-1α) stabilizer DMOG group. We found that the acetylcholine (ACh)-induced relaxation was dramatically reduced in pulmonary arteries from IR-injured rats compared with controls (P < 0.01). Interestingly, pre-treatment with the DMOG significantly improved ACh-stimulated pulmonary arterial dilatation (P < 0.01). The protein expression of HIF-1α in pulmonary artery was significantly down-regulated by IR injury (P < 0.01). Moreover, DMOG remarkably reversed IR-induced down-regulation of HIF-1α (P < 0.01). There was no difference in ACh-stimulated relaxation of endothelium-denuded or L-NMMA-treated pulmonary arteries among the three groups. The bioavailability of nitric oxide (NO) and the phosphorylation level of inducible NO synthase (iNOS) in pulmonary artery were significantly decreased by IR injury (both P < 0.01), which were reversed by DMOG (P < 0.05 or P < 0.01). In addition, the levels of superoxide in pulmonary artery were not affected by the IR injury as well as IR injury plus administration with DMOG. The present study demonstrated that HIF-1α contributes to pulmonary vascular dysfunction in lung IR injury.
authors.affiliation: Department of Anesthesiology, The Second Hospital of Shandong University 247 Beiyuan Road, Jinan 250033, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, The Second Hospital of Shandong University 247 Beiyuan Road, Jinan 250033, China.
authors.forename: Yanwu
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Operating Room, Jinan Central Hospital, Affiliated to Shandong University 105 Jiefang Road, Jinan 250013, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Qilu Hospital of Shandong University 107 Wenhua West Road, Jinan 250012, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Oral Health, Qianfoshan Hospital of Shandong Province, Affiliated to Shandong University 16766 Jingshi Road, Jinan 250014, China.
authors.forename: Wanlin
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The Second Hospital of Shandong University 247 Beiyuan Road, Jinan 250033, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Feng
mesh_terms: D000600:Amino Acids, Dicarboxylic / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006976:Hypertension, Pulmonary / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism*; D011655:Pulmonary Embolism / Q000150:complications / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism*
chemical_list: D000600:Amino Acids, Dicarboxylic; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C040947:oxalylglycine
keywords: Hypoxia-inducible factor 1 alpha; inducible nitric oxide synthase; ischemia-reperfusion injury; lung; pulmonary vascular dysfunction