NITRATES AND ANGINA-PECTORIS

The review discusses the mechanisms of action of the organic nitrates, nitrate tolerance, and the effects of nitrates in patients with stabl e angina pectoris. The nitrates are prodrugs that enter the vascular s mooth muscle, where they are denitrated to form the active agent nitri c oxide (NO). NO activates guanylate cyclase, which results in cyclic guanosine monophosphate (cGMP) production and vasodilation as a result of reuptake of calcium by the sarcoplasmic reticulum. NO is identical to endothelium-derived relaxing factor (EDRF), which induces vasodila tion, inhibits platelet aggregation, reduces endothelium adhesion, and has anticoagulant and fibrinolytic effects. Thus, the nitrates may be more than vasodilators and, in addition to reducing ischemia, may aff ect the process of atherosclerosis. The vascular effects of nitrates a re attenuated during sustained therapy. Although the basis for the phe nomenon of nitrate tolerance is not completely understood, sulfhydryl depletion as well as neurohormonal activation and increased plasma vol ume may be involved. The administration of N-acetylcysteine, angiotens in-converting enzyme (ACE) inhibitors, or diuretics do not consistentl y prevent nitrate tolerance. At present, intermittent nitrate therapy is the only way to avoid nitrate tolerance. The intermittent administr ation of nitrates, however, cannot provide continuous therapeutic bene fits, and thus monotherapy with nitrates is not suitable for many pati ents with stable angina pectoris.