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

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)H1928-H1935
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume299
Issue number6
DOIs
Publication statusPublished - 2010 Dec

Keywords

  • Coronary microcirculation
  • Endothelium-derived hyperpolarizing factors

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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