Selective ETA receptor antagonism with BQ-123 is insufficient to inhibit angioplasty induced neointima formation in the rat.
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.
Douglas
S A
SA
SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA.
Vickery-Clark
L M
LM
Louden
C
C
Ohlstein
E H
EH
D000800:Angioplasty, Balloon; D000818:Animals; D016893:Carotid Stenosis / Q000628:therapy*; D065128:Endothelin Receptor Antagonists; D007261:Infusions, Intra-Arterial; D007274:Injections, Intraperitoneal; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012008:Recurrence; D017539:Tunica Intima / Q000187:drug effects*
D065128:Endothelin Receptor Antagonists; D010456:Peptides, Cyclic; C072247:cyclo(Trp-Asp-Pro-Val-Leu)