Pharmacology of Nitrates in Relation to Antianginal Action

Abstract

The action of the nitrates has been investigated extensively since the original discovery of the antianginal effect more than 100 years ago. During that period, we have gone the full circle and even somewhat more. Initially the lowering of arterial pressure was considered the primary mechanism of action. Subsequently, the coronary dilator action was discovered, and emphasis swung to an action directly on the myocardial blood supply. Little was it appreciated that the coronary dilator action was fleeting and that there were different segments of the coronary arterial system. With the work of Gorlin, Brachfeld, and their co-workers [2, 7], showing that when nitroglycerin relieved the anginal episode, coronary blood flow was not increased, emphasis shifted back to the peripheral aspects. The more recent work of Ganz and Marcus [5] also emphasizes the peripheral action. Pacing-induced angina was relieved by intravenous but not by intracoronary nitroglycerin despite an increase in coronary flow after the coronary injection. Furthermore, many of the highly effective coronary dilators developed in recent years are not universally effective in the treatment of angina pectoris. However, recent work suggests that nitroglycerin alters the distribution of blood flow between the epicardium and endocardium and between normal and ischemic regions.