Role of endothelin-1 in neointima formation after endothelial removal in rabbit carotid arteries.

To investigate the role of local endothelin (ET)-1 in neointima formation, we performed a balloon denudation in the rabbit carotid artery. Four weeks after denudation, regeneration of endothelial cells was almost complete, and a marked intimal hyperplasia was observed. The tissue level of ET-1-like immunoreactivity was significantly increased even at 24 and 72 h after denudation and was 9.3 times higher than the control group in 4 wk. On the same time course, the proliferating cell nuclear antigen (PCNA)-positive cells clearly appeared. Receptor density values for 125I-ET-1 and 125I-IRL-1620 [ET-receptor subtype B (ETB)-selective ligand] bindings were significantly greater in the hyperplastic artery without changes in dissociation equilibrium constant values. The 125I-ET-1 binding sites not inhibited with BQ-123 [ET-receptor subtype A (ETA)-selective antagonist] were significantly increased in hyperplastic arteries. ETB receptors were more densely localized in the neointima. The chronic intravenous administration of BQ-123 at plasma concentrations sufficient to antagonize the ETA receptors had no effect on neointima formation and the appearance of PCNA-positive cells. We concluded from all results that ET-1 would be involved in neointima formation after endothelial removal and that the ETA receptors would not play a role in this process.