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.
Azuma
H
H
Department Medicinal Chemistry, Faculty of Medicine, Tokyo Medical and Dental University, Japan.
Hamasaki
H
H
Niimi
Y
Y
Terada
T
T
Matsubara
O
O
D000818:Animals; D002339:Carotid Arteries / Q000166:cytology / Q000502:physiology*; D016232:Endothelins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011817:Rabbits; D017466:Receptors, Endothelin / Q000378:metabolism; D012038:Regeneration; D017539:Tunica Intima / Q000737:chemistry / Q000502:physiology*
D016232:Endothelins; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D018809:Proliferating Cell Nuclear Antigen; D017466:Receptors, Endothelin; C074308:sovateltide; C072247:cyclo(Trp-Asp-Pro-Val-Leu)