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  • 1 Department of Cardiovascular Surgery, Semmelweis University Budapest, Hungary
  • | 2 Department of Cardiovascular Surgery, Semmelweis University Budapest, Hungary
  • | 3 Department of Cardiovascular Surgery, Semmelweis University Budapest, Hungary
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Endothelin elicits long-lasting vasoconstriction in the coronary bed. This remarkable spastic response raises the question whether or not the metabolic adaptive mechanisms of the coronaries are activated under endothelin effect. The role of the compensatory mediators adenosine and inosine was investigated before and after intracoronary (ic.) administration of endothelin-1 (ET-1, 1.0 nmol) using 1-min reactive hyperemia (RH) tests on in situ dog hearts (n=15) with or without blocking the ATP-sensitive potassium (K +ATP) channels by glibenclamide (GLIB, 1.0 mmol min –1, ic.). The release of adenosine and inosine via the coronary sinus was measured by HPLC during the first minute of RH. Endothelin-1 reduced baseline coronary blood flow (CBF) and RH response (hyperemic excess flow (EF) control vs. ET-1: 81.7±13.6 vs. 43.4±10.9 ml, P<0.01), while it increased the net nucleoside release (adenosine, control vs. ET-1: 58.9±20.4 vs. 113.7±39.4 nmol, P<0.05; inosine: 242.1±81.8 vs. 786.9±190.8 nmol, P<0.05). GLIB treatment alone did not change baseline CBF but also reduced RH significantly and increased nucleoside release (EF control vs. GLIB: 72.1±11.7 vs. 31.9±5.5 ml, P<0.01; adenosine: 18.8±4.6 vs. 63.0±24.8 nmol, P<0.05; inosine: 113.0±37.2 vs. 328.2±127.5 nmol, P<0.05). Endothelin-1 on GLIB-treated coronaries further diminished RH and increased nucleoside release (EF: 21.5±8.0 ml, P<0.05 vs. GLIB; adenosine: 75.3±28.1 nmol, NS; inosine: 801.9±196.6 nmol, P<0.05 vs. GLIB). The data show that ET-1 reduces metabolic adaptive capacity of the coronaries, and this phenomenon is due to decreased vascular responsiveness and not to the blockade of ischemic mediator release from the myocardium. The coronary effect of ET-1 may partially be dependent on K +ATP channels. _;

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