Selective ETA receptor antagonism with BQ-123 is insufficient to inhibit angioplasty induced neointima formation in the rat

Cardiovasc Res. 1995 May;29(5):641-6.

Abstract

Objective: The aim was to assess whether or not the endothelin ETA receptor selective antagonist BQ-123 could inhibit neointima formation in vivo following balloon angioplasty.

Methods: The effect of either acute administration of BQ-123 (0.1 mg.kg-1.min-1 intra-arterial infusion for 1 h before and 1 h after angioplasty) or chronic administration (bolus intraperitoneal injection, 2.5 mg.kg-1 twice daily; continuous intraperitoneal infusion, 0.8 and 8 mg.kg-1.d-1) on neointima formation was examined in rats which had undergone left common carotid artery balloon angioplasty.

Results: Neither acute intra-arterial infusion nor either mode of chronic intraperitoneal administration of BQ-123 had a significant effect on the degree of neointima formation observed following balloon angioplasty.

Conclusions: Neither acute nor chronic ETA receptor blockade is sufficient to inhibit angioplasty induced neointima formation in the rat. Since it was previously shown that the ETA/B antagonist SB 209670 was effective in this model, while the ETA selective antagonist BQ-123 is now found to be ineffective, the data implicate the ETB receptor subtype in the pathogenesis of neointima formation.

MeSH terms

  • Angioplasty, Balloon*
  • Animals
  • Carotid Stenosis / therapy*
  • Endothelin Receptor Antagonists*
  • Infusions, Intra-Arterial
  • Injections, Intraperitoneal
  • Male
  • Peptides, Cyclic / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Recurrence
  • Tunica Intima / drug effects*

Substances

  • Endothelin Receptor Antagonists
  • Peptides, Cyclic
  • cyclo(Trp-Asp-Pro-Val-Leu)