Different localization of ETA and ETB receptors in the hyperplastic vascular wall.

Abstract

We investigated which subtypes of endothelin-1 (ET-1) receptors are involved in the pathogenesis of angioplasty-induced lesion formation in the rabbit carotid artery. Four weeks after removing endothelial cells (EC), we noted a marked intimal hyperplasia. The Bmax values for [125I]ET-1 and [125I]IRL1620 (an agonist for the ETB receptors) bindings were greater in the hyperplastic artery, without changes in Kd values. [125I]ET-1 binding was completely inhibited by unlabeled ET-1 and Ro 46-2005, a mixed-type antagonist for the ETA and ETB receptors, but partially by BQ123, a selective antagonist for ETA receptors, and IRL1620. The [125I]ET-1 binding sites not inhibited with BQ123 were significantly increased in the hyperplastic artery. The binding study suggested the presence of non-ETA/non-ETB receptors. The rank order of the increasing ratio in the density of receptors was ETB > putative non-ETA/non-ETB > total ET-1 receptors > ETA. The histochemical experiments with biotinylated ET-1 at lysine-9 side chain alone or in combination with unlabeled ET-1, BQ123, Ro 46-2005, or IRL1620, showed the ETA receptors to be localized mainly in the media, whereas the ETB receptors localized mainly in the neointima. These results suggest that the increased ET-1 receptors, especially ETB and/or putative non-ETA/non-ETB, are closely related to the occurrence of the intimal hyperplasia after endothelial removal.

• Authors: H Azuma, H Hamasaki, J Sato, E Isotani, S Obayashi, O Matsubara
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 25 Issue 5 Pg. 802-9 (May 1995) ISSN: 0160-2446 [Print] United States
• PMID: 7630158 (Publication Type: Journal Article)

Chemical References

• Endothelins
• Peptide Fragments
• Peptides, Cyclic
• Pyrimidines
• Receptor, Endothelin A
• Receptor, Endothelin B
• Receptors, Endothelin
• Sulfonamides
• sovateltide
• Ro 46-2005
• cyclo(Trp-Asp-Pro-Val-Leu)

Topics

• Analysis of Variance
• Angioplasty (adverse effects)
• Angioplasty, Balloon (adverse effects)
• Animals
• Binding, Competitive (drug effects)
• Carotid Arteries (drug effects, pathology, ultrastructure)
• Endothelins (metabolism, pharmacology)
• Hyperplasia
• Male
• Microscopy, Electron, Scanning
• Muscle, Smooth, Vascular (drug effects, pathology, ultrastructure)
• Peptide Fragments (metabolism, pharmacology)
• Peptides, Cyclic (pharmacology)
• Pyrimidines (pharmacology)
• Rabbits
• Radioligand Assay
• Receptor, Endothelin A
• Receptor, Endothelin B
• Receptors, Endothelin (analysis, metabolism)
• Sulfonamides (pharmacology)