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 oxygen tension (PaO2). Red blood cells in Krebs-Henseleit buffer were oxygenated to obtain control and high-PaO2 perfusates. Arterial oxygen content was kept constant in both perfusates by reducing hemoglobin concentration in the high-PaO2 perfusate. Coronary blood flow was kept constant so that oxygen supply would not vary with the rise in PaO2. Increases in perfusion pressure therefore reflected increased coronary resistance. The high PaO2-induced coronary vasoconstriction was not affected by administration of indomethacin, nordihydroguaiaretic acid, NG-nitro-L-arginine, or superoxide dismutase and catalase but was abolished after endothelium damage or by cromakalim. These results demonstrate that 1) the endothelium contributes to the high PaO2-induced coronary vasoconstriction; 2) this effect is independent of cyclooxygenase or lipoxygenase products, nitric oxide, or free radicals; and 3) the closure of ATP-sensitive K+ channels mediates this vasoconstriction.