Contribution of endothelin-1 to warm ischemia/reperfusion injury of the rat lung.
The purpose of the present study was to clarify the role of endothelin-1 (ET-1) in the pathogenesis of ischemia/reperfusion lung injury and to determine whether pretreatment with an ET receptor antagonist prevents such injury. The left lung of Sprague-Dawley rats was subjected to 60 min of no-flow warm ischemia followed by 90 min of reperfusion. The plasma ET-1 concentration increased significantly after reperfusion compared with before and after ischemia (p < 0.05). Arterial oxygen tension was reduced, and the lung tissue wet/dry weight ratio increased in post-reperfusion lungs compared with both pre-ischemia and post-ischemia lungs. Histologic study showed pulmonary edema, hemorrhage, hyaline membrane formation, and a significant increase in lung tissue neutrophils after reperfusion. In addition, the expression of ET-1 mRNA was determined by Northern blot analysis. Although ischemia did not significantly alter ET-1 expression, reperfusion increased expression in the left lung markedly and in the right lung moderately. Pre-infusion of FR139317, an ETA receptor antagonist, prevented post-reperfusion damage to the lung. These results suggest that ET-1 contributes to the ischemia/reperfusion injury of the rat lung, mediated by an ETA receptor, and that an ETA receptor antagonist may inhibit ischemia/reperfusion lung injury.
Department of Surgery, Kobe University School of Medicine, Japan.
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Okada
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Yamashita
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Okada
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Okada
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D015152:Blotting, Northern; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000097:blood / Q000235:genetics / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology; D008168:Lung / Q000098:blood supply* / Q000473:pathology; D008297:Male; D009929:Organ Size; D010100:Oxygen / Q000097:blood; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood / Q000473:pathology / Q000503:physiopathology*
D001381:Azepines; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D007211:Indoles; D012333:RNA, Messenger; C079574:FR 139317; D010100:Oxygen