title: Contribution of nitric oxide in big endothelin-1-induced cardioprotective effects on ischemia/reperfusion injury in rat hearts.
abstract: We have recently shown that an appropriate amount of exogenous big endothelin-1 (ET-1) has beneficial effects on ischemia-/reperfusion-induced norepinephrine overflow and cardiac dysfunction in rat hearts and that these effects occur through a conversion to ET-1 by endothelin-converting enzyme and following stimulation of ETB receptor. In this study, we examined the possible involvement of nitric oxide (NO) in the big ET-1-induced cardioprotective effects. According to the Langendorff technique, isolated rat hearts were subjected to 40-minute global ischemia followed by 30-minute reperfusion. Exogenous big ET-1 (0.3 nM) significantly increased NOx (NO2/NO3) level in the coronary effluent after onset of reperfusion. This effect was markedly attenuated by treatment with SM-19712 (selective endothelin-converting enzyme inhibitor), A-192621 (selective ETB receptor antagonist), or NG-nitro-l-arginine (nonselective NO synthase inhibitor), respectively. In addition, N-nitro-l-arginine blunted big ET-1-induced suppression of norepinephrine overflow and improvement of cardiac dysfunction after ischemia/reperfusion. These findings suggest that NO produced by ETB receptor activation plays an important role in exogenous big ET-1-induced actions.
authors.affiliation: Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Tawa
authors.forename: Taiki
authors.initials: T
authors.lastname: Fukumoto
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ohkita
authors.forename: Naoto
authors.initials: N
authors.lastname: Yamashita
authors.forename: Ayman
authors.initials: A
authors.lastname: Geddawy
authors.forename: Takeshi
authors.initials: T
authors.lastname: Imamura
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Ayajiki
authors.forename: Tomio
authors.initials: T
authors.lastname: Okamura
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Matsumura
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D019332:Endothelin-1 / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044023:Receptor, Endothelin B / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D019332:Endothelin-1; D044023:Receptor, Endothelin B; D009569:Nitric Oxide; D009638:Norepinephrine