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Role of endothelin-1 receptor blockers on hemodynamic parameters and oxidative stress

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Abstract

Endothelin (ET) was first isolated and described by Yanagisawa et al. and has since been described as one of the most potent known vasoconstrictor compounds. ET-1 mediates its effects via two types of receptors, ETA and ETB, which are expressed in the vascular smooth muscle cells, endothelial cells, intestines and brain. Secretion of ET-1 results in long-lasting vasoconstriction, increased blood pressure and, in turn, overproduction of free radicals. As dysregulation of the endothelin system is an important factor in the pathogenesis of several diseases including atherosclerosis, hypertension and endotoxic shock, the ETA and ETB receptors are attractive therapeutic targets for treatment of these disorders. The biosynthesis and release of ET-1 are regulated at the transcriptional level. Studies have shown that p38MAP kinase, nuclear factor κB (NF-κB), PKC/ERK and JNK/c-Jun all take part in the ROS-activated production of ET-1. Furthermore, administration of ETA significantly reduces the generation of free radicals. However, treatment with ETB receptor blockers does not elicit the same effect. Therefore, the effects of endothelin receptor blockers on blood pressure and the generation of free radicals remain debatable. This review summarizes recent investigations into the role of endothelin receptor blockers with respect to the modulation of hemodynamic parameters and the generation of free radicals.

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Abbreviations

BP:

blood pressure

CAT:

catalase

DAG:

diacylglycerol

ET-1:

endothelin-1

ETA:

Rtype A of endothelin receptor

ETB:

Rtype B of endothelin receptor

HR:

heart rate

H2O2:

hydrogen peroxide

IP3:

inositol-3 phosphate

LPS:

lipopolysaccharide

MAP:

mean arterial pressure

MAPK:

mitogen-activated protein kinases

NF-κB:

nuclear factor κB

NO:

nitric oxide

O2·-:

superoxide anion

OH·:

hydrogen radical

ONOO-:

peroxynitrite

pp-ET-1:

pre-pro endothelin-1

ROS:

reactive oxygen species

SOD:

superoxide dismutase

TNF-α:

tumor necrosis factor-α

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Authors and Affiliations

  1. Chair of Experimental and Clinical Physiology, Department of Cardiovascular Physiology, Medical University of Ł’ódź, Mazowiecka 6/8, PL 92-215, Ł’ódź, Poland

    Aleksandra Piechota & Anna Gorąca

  2. Faculty of Process and Environmental Engineering, Technical University of Ł’ódź, Wólczańska 213/215, PL 90-924, Ł’ódź, Poland

    Andrzej Polańczyk

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  1. Aleksandra Piechota
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Piechota, A., Polańczyk, A. & Gorąca, A. Role of endothelin-1 receptor blockers on hemodynamic parameters and oxidative stress. Pharmacol. Rep 62, 28–34 (2010). https://doi.org/10.1016/S1734-1140(10)70240-1

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