MECHANISMS OF CORONARY VASOCONSTRICTION INDUCED BY HIGH ARTERIAL OXYGEN-TENSION

In isolated rabbit hearts perfused with suspension of red blood cells, we investigated the role of the endothelium and of several substances in the coronary vasoconstriction induced by a high arterial blood oxy gen tension (Pa-O2). Red blood cells in Krebs-Henseleit buffer were ox ygenated to obtain control and high-Pa-O2 perfusates. Arterial oxygen content was kept constant in both perfusates by reducing hemoglobin co ncentration in the high-Pa-O2 perfusate. Coronary blood flow was kept constant so that oxygen supply would not vary with the rise in Pa-O2. Increases in perfusion pressure therefore reflected increased coronary resistance. The high Pa-O2-induced coronary vasoconstriction was not affected by administration of indomethacin, nordihydroguaiaretic acid, N-G-nitro-L-arginine, or superoxide dismutase and catalase but was ab olished after endothelium damage or by cromakalim. These results demon strate that 1) the endothelium contributes to the high Pa-O2-induced c oronary vasoconstriction; 2) this effect is independent of cyclooxygen ase or lipoxygenase products, nitric oxide, or free radicals; and 3) t he closure of ATP-sensitive K+ channels mediates this vasoconstriction .