Contribution of nitric oxide in big endothelin-1-induced cardioprotective effects on ischemia/reperfusion injury in rat hearts.
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| 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.
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| Authors | Masashi Tawa, Taiki Fukumoto, Mamoru Ohkita, Naoto Yamashita, Ayman Geddawy, Takeshi Imamura, Kazuhide Ayajiki, Tomio Okamura, Yasuo Matsumura |
| Journal | Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 57 Issue 5 Pg. 575-8 (May 2011) ISSN: 1533-4023 [Electronic] United States |
| PMID | 21326108 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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