F.: Mode of action of nitroglycerin in angina pectoris

Nitroglycerin is generally agreed to be the most effective drug available for the treatment of angina pectoris, but its mode of action remains uncertain. Two main explanations have been put forwird. The first suggests that it acts by lowering the arterial pressure and so reducing cardiac work; the second that it acts by dilating the coronary arteries and so improving the myocardial blood supply. For many years the coronary dilator action of the drug has been widely accepted as the probable mechanism for its therapeutic effect, and its action in reducing blood pressure has been regarded as of secondary importance, if not actually harmful. Attempts to demonstrate a beneficial effect on coronary flow in patients with ischaemic heart disease, however, have met with no success, and it appears that sub-lingual nitroglycerin is unable to increase the myo-cardial blood supply when the coronary arteries are diseased (Gorlin et al., 1959; Bernstein et al., 1966). This failure to confirm the coronary dilator theory has led to renewed interest in the possibility that the drug acts by reducing cardiac work, but the evi-dence to support this view is inconclusive. Most studies of the effect of nitroglycerin on the circu-latory response to exercise have shown that the drug reduces arterial pressure both in normal subjects and in patients with ischaemic heart disease (Eldridge et al., 1955; Muller and R0rvik, 1958; Christensson, Karlefors, and Westling, 1965; Najmi et al., 1967). In none of these investigations, however, have the changes in the circulatory response been correlated with the alteration in capacity for exercise. In consequence, though it is generally accepted that nitroglycerin does cause some attenuation of the circulatory response to exercise, it has been impossible to assess the exten