Adrenomedullin infusion attenuates myocardial ischemia/reperfusion injury through the phosphatidylinositol 3-kinase/Akt-dependent pathway

Infusion of adrenomedullin (AM) has beneficial hemodynamic effects in patients with heart failure. However, the effect of AM on myocardial ischemia/reperfusion remains unknown. Male Sprague-Dawley rats were exposed to a 30-minute period of ischemia induced by ligation of the left coronary artery. Th...

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Veröffentlicht in:Circulation (New York, N.Y.) N.Y.), 2004-01, Vol.109 (2), p.242-248
Hauptverfasser: OKUMURA, Hiroyuki, NAGAYA, Noritoshi, TOYOKUNI, Shinya, YUTANI, Chikao, KANGAWA, Kenji, ITOH, Takefumi, OKANO, Ichiro, HINO, Jun, MORI, Kenji, TSUKAMOTO, Yoshitane, ISHIBASHI-UEDA, Hatsue, MIWA, Senri, TAMBARA, Keiichi
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Sprache:eng
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Zusammenfassung:Infusion of adrenomedullin (AM) has beneficial hemodynamic effects in patients with heart failure. However, the effect of AM on myocardial ischemia/reperfusion remains unknown. Male Sprague-Dawley rats were exposed to a 30-minute period of ischemia induced by ligation of the left coronary artery. They were randomized to receive AM, AM plus wortmannin (a phosphatidylinositol 3-kinase [PI3K] inhibitor), or saline for 60 minutes after coronary ligation. Hemodynamics and infarct size were examined 24 hours after reperfusion. Myocardial apoptosis was also examined 6 hours after reperfusion. The effect of AM on Akt phosphorylation in cardiac tissues was examined by Western blotting. Intravenous administration of AM significantly reduced myocardial infarct size (28+/-4% to 16+/-1%, P
ISSN:0009-7322
1524-4539
DOI:10.1161/01.CIR.0000109214.30211.7C