Relaxing and Contracting Factors in the Microcirculation
The five main determinants of coronary artery blood flow are: metabolic regulation, coronary perfusion pressure (auto-regulation), systolic compression, autonomic nervous system, and circulating substances and/or endothelial factors. Recent information on endothelial factors which regulate coronary blood flow are of interest to this meeting because of important interactions with molecular oxygen and with hemoglobin when used as a blood substitute for oxygen transport. Circulating substances/endothelial factors which alter coronary blood flow include catacholamines, prostacyclin, endothelial derived relaxant factor (EDRF, nitric oxide, NO), endothelial derived contracting factor, thromboxane A2, endothelin, angiotensin-2, vasopressin, and neuropeptide Y. Nitric oxide which activates guanylate cyclase directly is released by endothelial cells in response to shear as well as certain pharmacologic stimuli including: thrombin, acetylcholine bradykinin, endotoxin, FMET-LEU-PHE, leukotrienes, platelet activation factor, and some other non physiologic stimuli. Shear is an important initiator of EDRF release because of its role in auto-regulation. Through shear related NO release, other factors which cause large vessel coronary dilation, microvascular dilation or an increase in coronary perfusion pressure will result in increased vasorelaxation and a positive feedback cycle for coronary vasodilation. Thus, nitric oxide will counteract the intrinsic auto regulatory system which keeps blood flow constant when metabolic need is constant during changes in coronary perfusion pressure. Nitric oxide may also act as a feedback link between metabolically induced microvascular dilation and large vessel dilation, the signal being transmitted by increased shear.