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Effects of endothelins on cardiac and vascular cells: new therapeutic target for the future?
- Source :
-
Current vascular pharmacology [Curr Vasc Pharmacol] 2004 Jan; Vol. 2 (1), pp. 53-63. - Publication Year :
- 2004
-
Abstract
- The predominant isoform of the endothelin peptide family. endothelin-1 (ET-1) exerts various biological effects. These include effects on arterial smooth muscle cells causing intense vasoconstriction and stimulation of cardiac cells. ET-1 promotes changes in cardiomyocytes that are consistent with electrical remodelling such as changes in ionic current density and inhomogeneous prolongation of action potential duration resulting in increased dispersion. As for the underlying mechanisms, ET-1 was shown to suppress several cAMP-dependent ionic currents, such as ICa, IK and ICl in various mammalian cardiac preparations including human myocytes; however, the degree of suppression of these currents is different and highly dependent on experimental conditions. The proposed arrhythmogenic effects of ET-1 may also involve enhancement of Ca2+ release from intracellular stores, generation of IP3, and acidosis due to stimulation of the Na+/H+ exchange. Furthermore, ET-1 acts as the natural counterpart to endothelium-derived nitric oxide, which exerts vasodilator, antithrombotic and antiproliferative effects, and inhibits leukocyte adhesion to the vascular wall. Effects of ET-1 are mediated through interaction with two major types of cell surface receptors. ETA receptors have been associated with electrical remodelling, vasoconstriction and cell growth, while ETB receptors are involved in the clearance of ET-1, inhibition of endothelial apoptosis, release of NO and prostacyclins, and inhibition of the expression of ET-1 converting enzyme. The derangement of endothelial function in various cardiovascular diseases, such as cardiomyopathies, hypertension or arteriosclerosis, is a crucial element of the pathomechanism, thus ET receptors are considered as important therapeutic targets. Indeed, ET receptor antagonists may be able to preserve or restore endothelial integrity and may have antiarrhythmic properties; therefore, they are promising tools in cardiovascular medicine.
- Subjects :
- Animals
Electric Stimulation
Humans
Muscle, Smooth, Vascular metabolism
Muscle, Smooth, Vascular physiology
Myocytes, Cardiac metabolism
Protein Isoforms
Signal Transduction drug effects
Ventricular Fibrillation drug therapy
Calcium metabolism
Endothelin Receptor Antagonists
Endothelin-1 adverse effects
Endothelin-1 metabolism
Endothelin-1 physiology
Endothelins antagonists & inhibitors
Endothelins biosynthesis
Endothelins physiology
Muscle, Smooth, Vascular drug effects
Myocardial Contraction drug effects
Myocardial Contraction physiology
Myocytes, Cardiac drug effects
Vasoconstriction drug effects
Vasoconstriction physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1570-1611
- Volume :
- 2
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Current vascular pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 15320833
- Full Text :
- https://doi.org/10.2174/1570161043476528