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

J Cardiovasc Pharmacol. 1995 May;25(5):802-9. doi: 10.1097/00005344-199505000-00017.

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.

MeSH terms

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

Substances

  • 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)