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.
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.
Authors: Karolina M Duthie; Patrick W F Hadoke; Nicholas S Kirkby; Eileen Miller; Jessica R Ivy; John F McShane; Win Gel Lim; David J Webb Journal: Br J Pharmacol Date: 2015-04-23 Impact factor: 8.739