Role of mitochondrial oxidative phosphorylation in regulation of coronary blood flow.

Abstract

Regulation of coronary blood flow was studied in isolated rat hearts perfused under various metabolic conditions. Alterations in coronary flow were induced by hypoxia, amobarbital (Amytal) infusion, increase in work load of the heart, and adenosine infusion. Hypoxia induced, on the average, a 92.5% rise in coronary flow; 0.88 mM Amytal, a 85.7% increase; 12 microM adenosine, a 49.5% rise; and increased work load (elevation of the perfusion pressure from 6.9 kPa to 12.8 kPa), a 53.4% increase. In normoxia, adenosine, inosine, and hypoxanthine were present in the effluent in very low concentrations, and these greatly increased in response to hypoxia. In contrast, increased coronary flow caused by Amytal infusion or by elevated perfusion pressure was not accompanied by elevation in the effluent concentration of adenosine and its catabolites. Infusion of Amytal was followed by decrease in oxygen consumption of the heart and increase in oxygen tension in the effluent. This indicates that tissue oxygen tension per se can not be responsible for the regulation of coronary blood flow. Analysis of the data showed that under conditions in which there was a decrease in the tissue [ATP]free/[ADP]free[Pi] an increase in coronary flow was observed irrespective of the nature of the vasodilatory stimulus. It is concluded that mitochondrial oxidative phosphorylation provides a link between tissue oxygen metabolism and coronary blood flow. Mechanisms are discussed whereby changes in the cellular energy state ([ATP]free/[ADP]free[Pi]) are coupled to vasodilation, including possible direct effects on the vascular smooth muscle and/or generation of "second messengers."