title: Contribution of endogenous endothelin to the extension of myocardial infarct size in rats.
abstract: Pathophysiological roles of endogenous endothelin have been studied from the viewpoint of its contribution to the extension of myocardial infarct size. A monoclonal antibody against endothelin 1 (AwETN40) suppressed changes induced by endothelin 1 and endothelin 2 but did not modify those by endothelin 3 in vivo or in vitro. Effects of AwETN40 on myocardial infarct size were investigated. Coronary ligation (1 hour) and reperfusion (24 hours) in rats caused infarction in 35% of the left ventricle. Repetitive or single administration of AwETN40 reduced the infarct size; an intravenous injection of 22.5 mg/kg of the antibody 5 minutes after coronary occlusion or 5 minutes before reperfusion reduced the size by 38% or 31% of the control, respectively. Plasma and tissue endothelin 1 and plasma big endothelin 1 in rats were measured at various stages after occlusion. Plasma endothelin 1 showed a fourfold increase 10 minutes after reperfusion (from 1.02 to 3.96 pg/ml) and had returned to the control value after 8 hours. Plasma big endothelin 1 showed changes similar to those of plasma endothelin 1. No significant changes in plasma endothelin 2 and endothelin 3 were observed. Cardiac tissue contained seven times as much endothelin 1 as the control value 1 hour after reperfusion (4.59 versus 33.1 pg/g tissue), and a high concentration (13.2 pg/g tissue) was maintained even after 48 hours. We concluded that an increase in endogenous endothelin 1 plays an important role in the extension of myocardial infarct size.
authors.affiliation: Biology Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
authors.forename: N
authors.initials: N
authors.lastname: Suzuki
authors.forename: N
authors.initials: N
authors.lastname: Shimamoto
authors.forename: M
authors.initials: M
authors.lastname: Fujino
authors.forename: A
authors.initials: A
authors.lastname: Imada
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D016232:Endothelins / Q000032:analysis / Q000097:blood / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000737:chemistry; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014661:Vasoconstriction
chemical_list: D000911:Antibodies, Monoclonal; D016232:Endothelins