The cardiovascular continuum: from endothelial dysfunction to clinical events. The role of organic nitrates

Abstract

The endothelium plays a key role in the regulation of numerous physiological func- tions, including fibrinolysis, thrombosis, inflammation, cell growth and the maintenance of vas- cular tone. Several studies have shown that endothelial dysfunction is an early event in the course of the heart failure and changes in vascular reactivity have a series of hemodynamic con- sequences, including increases in total peripheral resistance and afterload, worsening of cardiac performance and a reduction in tolerance to exercise. Organic nitrates are the oldest drugs used in patients with coronary artery disease and heart fail- ure and are able to deliver nitric oxide (NO) directly to the vascular wall inducing the well known vasodilator effects. Therefore, it is likely that the release of NO by organic nitrates is associated with antiaggregato- ry, antiadhesive, antiproliferative and antioxidative effects, all of which are considered to be va- soprotective. Recent data from animal models suggest that treatment with high doses of isosorbide mononi- trate (ISMN) reduce the progression of atherosclerosis and this reduction of morphologic changes is associated with an improvement of the endothelial function. Organic nitrates and re- cent mononitrates (IS-5-MN and IS-2-MN) appear useful to protect arterial endothelium and in- hibit the progression of the disease in heart failure and ischemic heart disease. (Heart Interna- tional 2007; 3: 78-85)