l-Citrulline dilates rat retinal arterioles via nitric oxide- and prostaglandin-dependent pathways in vivo

l-Citrulline is an effective precursor of l-arginine produced by the l-citrulline/l-arginine cycle, and it exerts beneficial effects on the cardiovascular system by supporting enhanced nitric oxide (NO) production. NO dilates retinal blood vessels via the cyclooxygenase-mediated pathway. The purpose of this study was to examine the effects of l-citrulline on retinal circulation and to investigate the potential involvement of NO and prostaglandins in l-citrulline-induced responses in rats. l-Citrulline (10–300 μg kg−1 min−1, i.v.) increased the diameter of retinal arterioles without significantly changing mean blood pressure, heart rate, and fundus blood flow. The vasodilator response of retinal arterioles to l-citrulline was significantly diminished following treatment with NG-nitro-l-arginine methyl ester (30 mg/kg, i.v.), an NO synthase inhibitor, or indomethacin (5 mg/kg, i.v.), a cyclooxygenase inhibitor. In addition, α-methyl-dl-aspartic acid (147 mg/kg, i.v.), an inhibitor of argininosuccinate synthase, the rate-limiting enzyme for the recycling of l-citrulline to l-arginine, diminished the l-citrulline-induced retinal vasodilation. These results suggest that both NO- and prostaglandin-dependent pathways contribute to the l-citrulline-induced vasodilation of rat retinal arterioles. The l-citrulline/l-arginine recycling pathway may have more importance in regulating vascular tone in retinal blood vessels than in peripheral resistance vessels.