Role of endothelin-1 receptor blockers on hemodynamic parameters and oxidative stress.
Journal Title: Pharmacological Reports - Year 2010, Vol 62, Issue 1
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 kappaB (NF-kappaB), PKC/ERK and JNK/c-Jun all take part in the ROS-activated production of ET-1. Furthermore, administration of ET(A) 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.
Authors and Affiliations
Aleksandra Piechota, Andrzej Polańczyk, Anna Gorąca
Keywords
Related Articles
- EP ID EP134263
- DOI -
- Views 102
- Downloads 0
Humanins, the neuroprotective and cytoprotective peptides with antiapoptotic and anti-inflammatory properties.
Humanin (HN) is a newly discovered 24-amino acid peptide, which may suppress neuronal cell death. HN cDNA includes an open reading frame (HN-ORF) of 75 bases located 950 bases downstream of the 5' end of the HN cDNA. It...
Modulatory effects of sesamol in dinitrochlorobenzene-induced inflammatory bowel disorder in albino rats.
Background: Inflammatory bowel disease (IBD) is a chronic inflammatory condition of gastrointestinal tract of immune, genetic and environmental origin. In the present study, we examined the effect of sesamol (SES), the m...
Isolated rat inferior mesenteric artery response to adenosine: possible participation of Na(+)/K(+)-ATPase and potassium channels.
Adenosine (10(-7)-3 x 10(-4) M) produced concentration-dependent and endothelium-independent relaxation of isolated rat inferior mesenteric artery. Application of indomethacin (10(-5) M) or N(G)-nitro-L-arginine (10(-5)...
Neuroprotective potential of mGluR5 antagonist MTEP: effects on kainate-induced excitotoxicity in the rat hippocampus.
Extensive research into glutamate receptors in the central nervous system has shown important role of metabotropic glutamate receptors (mGluR) as potential targets for neuroprotective drugs. The aim of the present study...
Cytisine for the treatment of nicotine addiction: from a molecule to therapeutic efficacy.
Cytisine, a natural plant alkaloid, has been marketed in Central and Eastern Europe for over 40 years for the clinical management of smoking cessation. Despite the fact that cytisine has been used by millions of smokers,...