The selective endothelin ETA receptor antagonist FR139317 inhibits neointimal thickening in the rat

Endothelin is known as a potent mitogenic mediator. We tested the in vivo ability of FR139,317((R)2-[(R)-2-[(S)-2-[[1-(hexahydro- 1H-azepinyl)]carbonyl]amino-4-methylpentanoyl] amino-3-[3-(1-methyl-1 H-indoyl)]propionyl]amino-3-(2-pyridyl)propionic acid), a selective antagonist of the endothelin ETA receptor subtype, to inhibit neointimal thickening following photochemically induced injury of the endothelium of rat femoral artery. FR139,317 (32 mg/kg s.c., twice a day) was administered for 3 weeks after the injury. FR139,317 significantly decreased the neointimal area (76.3%) without changing the medial area. Therefore, it is suggested that endothelin may play an important role, via mainly endothelin ETA receptors, in neointima formation in injured artery.