Effects of endothelins on cardiac and vascular cells: New therapeutic target for the future?

Attila Mohácsi, János Magyar, Tamás Bányász, Péter P. Nánási

Research output: Contribution to journalReview article

28 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)53-63
Number of pages11
JournalCurrent Vascular Pharmacology
Volume2
Issue number1
DOIs
Publication statusPublished - Jan 1 2004

Keywords

  • Blood vessels
  • Cardiac contractility
  • Endothelins
  • Heart diseases
  • Ion currents
  • Signal transduction
  • Vascular diseases

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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