Interdependence of pharmacologically-induced and endothelium-mediated coronary vasodilation in antianginal therapy

Abstract

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.

The anti‐diabetic drug miglitol is protective against anginal ischaemia through a mechanism independent of regional myocardial blood flow in the dog

“…19,20 In the present study, we measured RMBF using microspheres, a widely accepted method to measure myocardial blood flow, in order to assess whether miglitol affected RMBF. 10,21 However, miglitol did not change RMBF in the risk area, suggesting that miglitol does not have a vasodilating effect.…”

Nitrate: Warum und wie sie heute eingesetzt werden sollten

“…Nitrate setzen NO frei und ftihren somit ebenfalls zu einem Anstieg von zyklischem Guanosin-Monophosphat (Einzelheiten werden unten er6rtert). Im Gegensatz dazu ist die vasodilatatorische Wirksamkeit der Nitrate unabhfingig von der Unverletztheit des Endothels und kann sogar erh6ht sein, wenn das Endothel fehlt [111]. Auch eine Dehnung alleine scheint EDRF freizusetzen, wodurch die auf einen erhOhten Blutflug folgende, deutlich ausgeprfigte Vasodilatation erklfirt werden kann [107].…”

Potential role of coronary vasoconstriction in ischaemic heart disease: effect of exercise

“…The effect of 2-3 mg intracoronary diltiazem on coronary vasomotion of normal and stenotic vessel segments was evaluated in a third group of nine patients with coronary artery disease' 131 and compared with the data from 12 patients with coronary artery disease not given pretreatment prior to the exercise test' 11 . Intracoronary administration of diltiazem was associated with coronary vasodilation of the normal (+14%, P<001 vs rest) and stenotic (+15%, NS vs rest) vessel segment which was, however, slightly less than after intracoronary nitroglycerin (Figs 3 and 4).…”