Erythropoietin enhances hydrogen peroxide-mediated dilatation of canine coronary collateral arterioles during myocardial ischemia in dogs in vivo

Toyotaka Yada, Hiroaki Shimokawa, Osamu Hiramatsu, Minoru Satoh, Naoki Kashihara, Aya Takaki, Masami Goto, Yasuo Ogasawara, Fumihiko Kajiya

研究成果: Article査読

7 被引用数 (Scopus)

抄録

We have previously demonstrated that endothelium-derived hydrogen peroxide (H 2O 2) plays an important role in the canine coronary microcirculation as an endothelium-derived hyperpolarizing factor in vivo. However, it remains to be examined whether endogenous H 2O 2 is involved in the dilatation of coronary collaterals during myocardial ischemia in vivo and, if so, whether erythropoietin (EPO) enhances the responses. Canine subepicardial native collateral small arteries (CSA; ≥ 100 μm) and arterioles (CA; <100 μm) were observed using an intravital microscope. Experiments were performed after left anterior descending coronary artery ischemia (90 min) under the following eight conditions (n = 5 each): control, EPO, EPO+catalase, EPO+N-monomethyl-L-arginine (L-NMMA), EPO+L-NMMA+catalase, EPO+L-NMMA+ iberiotoxin [Ca 2+-activated K + (K Ca) channel blocker], EPO+L-NMMA +apamin+charybdotoxin (K Ca channel blocker), and EPO+wortmannin (phosphatidylinositol 3-kinase inhibitor). Myocardial ischemia caused significant vasodilatation in CA but not in CSA under control conditions, which was significantly decreased by catalase in CA. After EPO, the vasodilatation was significantly increased in both sizes of arteries and was significantly decreased by catalase. The enhancing effect of EPO was reduced by L-NMMA but not by catalase in CSA and was reduced by L-NMMA+catalase in CA, where the greater inhibitory effects were noted with L-NMMA+catalase, L-NMMA+iberiotoxin, L-NMMA+apamin+charybdotoxin, or wortmannin. EPO significantly ameliorated ischemia-induced impairment of myocardial Akt phosphorylation, which was abolished by L-NMMA+catalase or wortmannin. EPO also ameliorated oxidative stress and myocardial injury, as assessed by plasma 8-hydroxydeoxyguanosine and troponin-T, respectively. These results indicate that EPO enhances H 2O 2-mediated dilatation of coronary collateral arterioles during myocardial ischemia in dogs in vivo.

本文言語English
ページ(範囲)H1928-H1935
ジャーナルAmerican Journal of Physiology - Heart and Circulatory Physiology
299
6
DOI
出版ステータスPublished - 2010 12

ASJC Scopus subject areas

  • 生理学
  • 循環器および心血管医学
  • 生理学(医学)

フィンガープリント

「Erythropoietin enhances hydrogen peroxide-mediated dilatation of canine coronary collateral arterioles during myocardial ischemia in dogs in vivo」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル