[The mechanism of action of nitrates, 1988 status].
Nitrates are old drugs, introduced into medical treatment more than 100 years ago, initially as a homeopathic remedy against headache (1850), and only later against angina pectoris (1867). Their typical hemodynamic, antiischemic effects were described in man in the 1950s and 1960s. They include: a reduction in venous return, lowering of the abnormally increased left ventricular enddiastolic pressure during ischemia, a decrease in left ventricular systolic wall stress, and changes in left ventricular geometry resulting in a decrease of myocardial oxygen consumption. The vasodilatory effect on large epicardial coronary arteries, especially on eccentric stenoses through relaxation of vascular smooth muscle tone was described even more recently (1980). This effect proved to be of considerable clinical importance both in angina at rest, that is during a primary increase in vasomotor tone (coronary artery spasm) as well as in angina provoked by exercise, where the increase in vasomotor tone and in the degree of stenosis is often due to a rise in alpha-sympathetic tone. The relaxing effect on the large coronary arteries is regarded as additive to the one on venous tone. The real clinical importance of nitrates became, however, evident only in the last decade with the discovery of EDRF, the so-called endothelial-derived relaxing factor, an endogenous compound of endothelial origin at least partly consisting of nitrous oxide and therefore, like nitrates, it exerts its effect through the stimulation of cGMP. The tendency for coronary arteries to constrict in presence of atherosclerosis is explained by the lack of EDRF, especially in the region of atherosclerotic plaques where the endothelium is often absent or has lost its endocrine function.(ABSTRACT TRUNCATED AT 250 WORDS)
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Abteilung für klinische Kardiologie, Department für Innere Medizin, Medizinische Hochschule Hannover.
D000787:Angina Pectoris / Q000188:drug therapy; D000818:Animals; D003327:Coronary Disease / Q000188:drug therapy*; D004730:Endothelium, Vascular / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009566:Nitrates / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000502:physiology; D005996:Nitroglycerin / Q000627:therapeutic use; D014655:Vascular Resistance / Q000187:drug effects
D009566:Nitrates; D009569:Nitric Oxide; D005996:Nitroglycerin
Wirkungsmechanismus der Nitrate, Stand 1988.