Flow-dependent vasodilation in the coronary circulation: alterations in diseased states.

Abstract

Flow-dependent vasodilation has been recognized to play an important role in the perfusion of the myocardium and the occurrence of myocardial ischaemia. In the past few years, the role of the endothelium in the regulation of coronary artery dimensions has gained a lot of attraction. Changes in coronary artery size are caused through the contraction and relaxation of the smooth musculature within the vessel wall. Vasoactive substances released from the endothelium play a crucial role in the regulation of vessel size and coronary vasomotor tone. During physiologic exercise, normal coronary arteries dilate, whereas stenotic arteries constrict. This abnormal behaviour of the stenotic artery has been associated with the occurrence of myocardial ischaemia, and has been thought to be either due to: endothelial dysfunction with reduced release or production of the endothelial derived relaxant factor (EDRF); an increased sympathetic stimulation during exercise; enhanced platelet aggregation with release of thromboxane A2 and serotonin; and/or a passive collapse of the disease-free vessel segment within the stenosis when blood-flow velocity increases during exercise. Thus, a diseased coronary endothelium may have a dramatic effect on the function of the coronary arteries, and may cause or contribute to the occurrence of myocardial ischaemia under high-demand situations, e.g. physical exercise or mental stress. Changes in flow-dependent vasodilation have been described in various disease states, e.g. hypercholesterolaemia, hypertension, diabetes mellitus, but also in valvular heart disease, heart failure and transplantation. Most of these alterations are due to functional changes of the endothelium, but vascular remodelling of the coronary arteries with thickening of the intima and an enlargement of the artery may affect these functional changes importantly.