Coronary microcirculation - Physiology and pharmacology

Coronary microvessels play a pivotal role in determining the supply of oxyg en and nutrients to the myocardium by regulating the coronary flow conducta nce and substance transport. Direct approaches analyzing the coronary micro vessels have provided a large body of knowledge concerning the physiologica l and pharmacological characteristics of the coronary circulation, as has t he rapid accumulation of biochemical findings about the substances that med iate vascular functions. Myogenic and flow-induced intrinsic vascular contr ols that determine basal tone have been observed in coronary microvessels i n vitro. Coronary microvascular responses during metabolic stimulation, aut oregulation, and reactive hyperemia have been analyzed in vivo, and are kno wn to be largely mediated by metabolic factors, although the involvement of other factors should also be taken into account. The importance of ATP-sen sitive K+ channels in the metabolic control has been increasingly recognize d. Furthermore, many neurohumoral mediators significantly affect coronary m icrovascular control in endothelium-dependent and -independent manners. The striking size-dependent heterogeneity of microvascular responses to all of these intrinsic, metabolic, and neurohumoral factors is orchestrated for o ptimal perfusion of the myocardium by synergistic and competitive interacti ons, The regulation of coronary microvascular permeability is another impor tant factor for the nutrient supply and for edema formation. Analyses of co llateral microvessels and subendocardial microvessels are important for und erstanding the pathophysiology of ischemic hearts and hypertrophied hearts. Studies of the microvascular responses to drugs and of the impairment of c oronary microvessels in diseased conditions provide useful information for treating microvascular dysfunctions. In this article, the endogenous regula tory system and pharmacological responses of the coronary circulation are r eviewed from the microvascular point of view. (C) 2000 Elsevier Science Inc . All rights reserved.