▸ We discuss the mechanisms of the anti-ischemic actions of organic nitrates. ▸ We discuss side effects of chronic nitrate therapy like nitrate tolerance and endothelial dysfunction. ▸ We provide evidence for a role of nitrates in the phenomenon of ischemic preconditioning.
Despite the continuous development of newer drugs, the therapy of coronary artery disease remains challenging. Organic nitrates are among the oldest drugs, but they still remain a widely used adjuvant in the treatment of symptomatic coronary artery disease. While their efficacy in relieving angina pectoris symptoms in acute settings and in preventing angina before physical or emotional stress is undisputed, the chronic use of nitrates has been associated with potentially important side effects such as tolerance and endothelial dysfunction. The identification of the mitochondrial aldehyde dehydrogenase as the enzyme responsible for the bioactivation of nitroglycerin has allowed the formulation of a complex but plausible hypothesis regarding the mechanism of action and the development of the side effects associated with nitrate therapy. Further, the discovery of important differences among nitrates suggests that these drugs should not be considered as a homogeneous class. Finally, the identification of nonhemodynamic properties of nitrates, and newer insight on the mechanism of nitrate tolerance, have led us to question the prognostic impact of these drugs.