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: Xin Zhao, Yanwu Jin, Haibo Li, Zhigang Wang, Wanlin Zhang, Chang Feng
• Journal: International journal of clinical and experimental pathology (Int J Clin Exp Pathol) Vol. 7 Issue 6 Pg. 3081-8 ( 2014) ISSN: 1936-2625 [Electronic] United States
• PMID: 25031727 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acids, Dicarboxylic
• Hif1a protein, rat
• Hypoxia-Inducible Factor 1, alpha Subunit
• oxalylglycine

Topics

• Amino Acids, Dicarboxylic (pharmacology)
• Animals
• Blotting, Western
• Disease Models, Animal
• Endothelium, Vascular (drug effects, metabolism)
• Hypertension, Pulmonary (metabolism)
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Male
• Pulmonary Artery (drug effects, metabolism)
• Pulmonary Embolism (complications, metabolism)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (metabolism)