Praxis Medica (Jan 2014)
Endothelins as mediators in the modulation of cardiac performance
Abstract
The role of endothelin in cardiovascular physiology and pathophysiology has been undeniable ever since its discovery. Endothelins in the heart are important for the development, growth and remodeling, as well as for the control of contractility and rhythm. Cardiac endothelial cells in the endocardium and myocardial capillaries represent the main source of endothelin, and cardiomyocytes are their primary targets. Endothelin-1 is one of the most potent substances with a positive inotropic effect known to man; subsequently endothelin plays a key role in the cardiac endothelial-myocardial interaction. The endothelins are a family of 21 amino acid peptidesof which there are three distinct isoforms endothelin-1, endothelin-2 and endothelin-3. Their effects are achieved by the activation of endothelin receptors, ETA and ETB, which belonging to the family of G protein-linked receptors. ETA and ETB receptors are densely distributed in cardiomyocytes, the cells of the cardiovascular system, coronary vascular and endocardial endothelial cells. Under physiological conditions, endothelin is synthesized in endothelial cells, while under pathophysiological conditions in the large number of non-endothelial cells of the heart as well. Endothelin-1 has positively inotropic and chronotropic effects. The administration of ET-1 causes coronary vasoconstriction, leads to myocardial ischemia and a lethal ventricular arrhythmia. In the acute myocardial infarction, ET-1 increases myocardial necrosis and arrhythmia but has a favorable effect on heart recovery after a myocardial infarction at an early stage of cardiac remodeling. ET-1 reverses acidosis-induced negative lusitropic and inotropic effects without the increase of intracellular calcium. Endothelin can resist the arrhythmogenic effects of catecholamines. Thus, low concentrations of endothelin have a protective effect on the heart. Primary indications for the administration of endothelin antagonists are heart failure, pulmonary hypertension and resistant arterial hypertension. Careful and well-designed clinical studies are needed to verify the therapeutic potential of new types of drugs in cardiovascular medicine.
Keywords
