AJP - Heart and Circulatory Physiology, Vol 243, Issue 2 159-H169, Copyright © 1982 by American Physiological Society
Role of mitochondrial oxidative phosphorylation in regulation of coronary blood flow
E. M. Nuutinen, K. Nishiki, M. Erecinska and D. F. Wilson
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."
