[Milestones of cardiovascular therapy. III. Nitroglycerin].

Organic nitrates still constitute, like digitalis, an indispensable remedy. Amyl nitrite, discovered by Balard was the first to be used for the therapy of angina pectoris by Sir T. Lauder Brunton in 1867. Nitroglycerin (Glyceroltrinitrate) was synthetized by Ascanio Sobrero 1846 and was studied by Brunton, Tate, and Murrel who published his paper on the treatment of angina pectoris in 1879. It has been soon recognised that the main effect of nitrates is vasodilatation more pronounced in the veins, resulting in reduced venous return, decrease of left and right ventricular end-diastolic pressure and volume and in a reduction in the myocardioal oxygen demand. Sir William Osler was the first who suggested the use of nitroglycerin in patients with congestive heart failure "when the pulse is hard and firm", in his "Principles and Practice of Medicine" 1892. About fifty years later, L. Goldberg confirmed the antihypertensive effect of isosorbide dinitrate in a double--leticin trial on hypertensive patients. The long acting nitrates isosorbide dinitrate and isosorbide 5-mononitrate now share all the beneficial effects of nitroglycerin in patients with stable and unstable angina and in selected patients with heart failure. The sustained-release tablets of isosorbide 5-mononitrate have been shown to be effective with long-term use without inducing tolerance. The author also summaries basic data concerning the chemistry, pharmacology and clinical applications of organic nitrates and nitrocompounds. The position of nitrates in the treatment of isolated systolic hypertension in the elderly and of chronic heart failure is still to be established.