title: L-Citrulline dilates rat retinal arterioles via nitric oxide- and prostaglandin-dependent pathways in vivo.
abstract: 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 N(G)-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.
authors.affiliation: Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan. Electronic address: moria@pharm.kitasato-u.ac.jp.
authors.forename: Asami
authors.initials: A
authors.lastname: Mori
authors.affiliation: Healthcare Products Development Center, KYOWA HAKKO BIO CO., LTD, 2 Miyukigaoka, Tsukuba-shi, Ibaraki, 305-0841, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Morita
authors.affiliation: Healthcare Products Development Center, KYOWA HAKKO BIO CO., LTD, 2 Miyukigaoka, Tsukuba-shi, Ibaraki, 305-0841, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Morishita
authors.affiliation: Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakamoto
authors.affiliation: Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakahara
authors.affiliation: Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
authors.forename: Kunio
authors.initials: K
authors.lastname: Ishii
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism; D001124:Argininosuccinate Synthase / Q000037:antagonists & inhibitors; D002956:Citrulline / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism* / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011453:Prostaglandins / Q000378:metabolism* / Q000502:physiology*; D017208:Rats, Wistar; D012161:Retinal Artery / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D002956:Citrulline; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D001124:Argininosuccinate Synthase; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin
keywords: Cyclooxygenase; L-Citrulline; Nitric oxide; Retinal blood vessel