This study investigates the role of endothelial nitric oxide synthase (eNOS) in modulating angiogenesis in response to tissue ischemia using two animal models. In the first model, rabbits with operatively induced hindlimb ischemia were administered L-arginine, which significantly improved angiogenesis compared to placebo-treated controls. The second model used mice with targeted disruption of the eNOS gene, which showed impaired angiogenesis compared to wild-type controls. These findings suggest that eNOS acts downstream from vascular endothelial growth factor (VEGF) and that promoting eNOS activity through L-arginine supplementation can accelerate angiogenesis. The results indicate that defective endothelial NO synthesis may limit angiogenesis in patients with endothelial dysfunction related to atherosclerosis, and that oral L-arginine supplementation could be a potential therapeutic strategy for accelerating angiogenesis in patients with advanced vascular obstruction.This study investigates the role of endothelial nitric oxide synthase (eNOS) in modulating angiogenesis in response to tissue ischemia using two animal models. In the first model, rabbits with operatively induced hindlimb ischemia were administered L-arginine, which significantly improved angiogenesis compared to placebo-treated controls. The second model used mice with targeted disruption of the eNOS gene, which showed impaired angiogenesis compared to wild-type controls. These findings suggest that eNOS acts downstream from vascular endothelial growth factor (VEGF) and that promoting eNOS activity through L-arginine supplementation can accelerate angiogenesis. The results indicate that defective endothelial NO synthesis may limit angiogenesis in patients with endothelial dysfunction related to atherosclerosis, and that oral L-arginine supplementation could be a potential therapeutic strategy for accelerating angiogenesis in patients with advanced vascular obstruction.