Nitrates: New Insights into Old Drugs

Abstract

Nitric oxide (NO), a highly unstable gas with a half-life of a few seconds, is the most important mediator produced by endothelial cells and has several important protective functions concerning the control of vascular tone, thrombogenesis, fibrinolysis, cell proliferation, inflammation and endothelial permeability, which are crucial for the maintenance of an anti-inflammatory anti-atherogenic and anti-thrombotic state. The exogenous administration of NO with nitrates has been proposed as possible NO exogenous sources in endothelial dysfunction therapy and coronary artery disease because of their anti-atherosclerotic effect, through a reduction in oxidative stress, on low-density lipoprotein (LDL) oxidation, chemotactic molecules and growth factors, which mediate leukocytal adhesion and proliferation of vascular smooth cells. Moreover, nitrates show a vasodilatant effect on the venous, arterial and coronary region with a consequent reduction in preload, afterload and an improvement in myocardial energetic metabolism. Due to these favorable effects nitrates are indicated not only in angina pectoris, acute myocardial infarction and pulmonary hypertension or hypertension crisis, but also in systolic and diastolic heart failure, in the prevention of ischemic and reperfusion damage after IMA or PCI and in the prevention of post-infarctual remodeling. Moreover, recent data concerning the protective effects of nitrates on endothelial function, suggest their possible use in the prevention of endothelial damage and atherogenesis.