Release of endothelin during reperfusion of ischemic myocardium. ET-1 release from reperfused heart.
Endothelin, the most potent endothelium-derived vasoconstrictor, was found to be released from the isolated ischemic rat heart after a prolonged period of reperfusion. No endothelin release was observed up to 1 hour of reperfusion following 30 minutes of global ischemic arrest. Although most of the endothelin release occurred as a burst after 1 hour of reperfusion, the endothelin release increased progressively at a slower rate up to 2 hours of reperfusion. The calcium slow channel blocker, nifedipine, and the phospholipase inhibitor, mepacrine, but not the free radical scavengers, superoxide dismutase (SOD) and catalase, prevented the endothelin release from the heart. Unlike endothelin release that did not occur until after 1 hour of reperfusion, lipid peroxidation assessed by thiobarbituric acid reactive product formation, and cellular injury as monitored by creatine kinase (CK) release, occurred upon reperfusion, and increased progressively with the duration of reperfusion. All the interventions including nifedipine, mepacrine, and SOD plus catalase, prevented the lipid peroxidation and CK release significantly. Coronary flow was reduced significantly after 1 hour of reperfusion, when endothelin release occurred, an event that also coincided with myocardial endothelial injury as assessed by transmission electron microscopy. These results indicate that endothelin is released only after a prolonged period of reperfusion, and the release process seems to be controlled by calcium and phospholipase, but not by free radicals.
Maulik
N
N
Department of Surgery, University of Connecticut School of Medicine, Farmington 06030.
Liu
X
X
Subramanian
R
R
Das
D K
DK
D000704:Analysis of Variance; D000818:Animals; D003326:Coronary Circulation / Q000502:physiology; D003402:Creatine Kinase / Q000378:metabolism; D016232:Endothelins / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains
D016232:Endothelins; D003402:Creatine Kinase