Interdependence of pharmacologically-induced and endothelium-mediated coronary vasodilation in antianginal therapy.
Recent advances in the understanding of vascular physiology have furnished new aspects in the treatment of angina pectoris by various vasodilators. Upon stimulation by various factors (viscous drag from increased flow, pulsatile stretch, ADP/ATP, norepinephrine, serotonin), the coronary endothelium releases a vasodilator called endothelium-derived relaxant factor (EDRF). This factor has recently been shown to probably be nitric oxide (NO), which is identical to the active compound of nitroglycerin. EDRF (NO) dilates both large epicardial arteries and also coronary resistance vessels. It also has a strong platelet antiaggregant effect. The predominant effect of Ca2+ antagonists is on resistance vessels, increasing myocardial perfusion and viscous drag acting upon the endothelial lining. This, in turn, stimulates EDRF (NO) release in epicardial arteries and dilation. This additional nitrate-like effect augments the direct vasodilator effect of Ca2+ antagonists. Lack of normal endothelial function results in diminished capacity to dilate, and sometimes even in a shift from dilator to constrictor effects, paralleled by an increased tendency for platelet adhesion, activation, and thrombosis, which is still enhanced when plasma low density lipoprotein (LDL) is augmented. EDRF release, vasodilator capacity, and antiaggregant effects are reduced when LDL is high. Nitrates have a direct, endothelium-independent dilator effect, particularly on large coronary arteries, which seems even more pronounced when the endothelium is absent, but only when the vessel segment is still compliant. Therefore nitrates may particularly be effective in vessels with deficient EDRF release.
Bassenge
E
E
Department of Applied Physiology, University of Freiburg, West Germany.
Stewart
D J
DJ
D000787:Angina Pectoris / Q000188:drug therapy* / Q000503:physiopathology; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D009566:Nitrates / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D009566:Nitrates