Superoxide dismutase enhances both adenosine release and coronary hyperemic flow through protection of 5'-nucleotidase against its degradation during reperfusion following ischemia in dogs.

Abstract

Oxygen-derived free radicals are thought to inactivate ectosolic enzymes that regulate myocardial cellular functions. One such enzyme is ecto-5'-nucleotidase, which is responsible for adenosine production during coronary hyperemic flow. In the present study, we measured both reactive and hyperemic flow and adenosine release during reperfusion with and without superoxide dismutase. In 10 open chest dogs, the left anterior descending coronary artery was perfused through an extracorporeal bypass tube from the carotid artery. In the control hearts, a five-minute occlusion of the coronary artery caused the hyperemic flow with increased release of adenosine. In the superoxide dismutase-treated hearts, although administration of superoxide dismutase altered neither adenosine release nor coronary blood flow in the baseline, it augmented both peak coronary blood flow and repayment, and adenosine release during reperfusion. Therefore, we hypothesized that superoxide dismutase reduces generation of oxygen-derived free radicals during ischemia and reperfusion and attenuates the degradation of ecto-5'-nucleotidase. The administration of superoxide dismutase enhanced the increase in ecto-5'-nucleotidase activity at 10 minutes after reperfusion over the untreated group. Thus, we conclude that superoxide dismutase enhances reactive hyperemic flow and adenosine release during reperfusion following ischemia, which may be attributable to the protection of ecto-5'-nucleotidase by superoxide dismutase during ischemia and reperfusion.