title: Attenuation of nitric oxide- and prostaglandin-independent vasodilation of retinal arterioles induced by acetylcholine in streptozotocin-treated rats.
abstract: Diabetes alters retinal hemodynamics, but little is known about the impact of diabetes on the role of endothelium-derived hyperpolarizing factor (EDHF) in the regulation of retinal circulation. Therefore, we examined how diabetes affects the nitric oxide- and prostaglandin-independent vasodilation of retinal arterioles induced by acetylcholine. Male Wistar rats were treated with streptozotocin (80 mg/kg, i.p.) and experiments were performed 6-8 weeks later. Under artificial ventilation, rats were treated with tetrodotoxin (100 microg/kg, i.v.) to eliminate any nerve activity and prevent movement of the eye. Methoxamine was used to maintain adequate systemic circulation. Fundus images were captured by a digital camera that was equipped with a special objective lens. The vasodilator responses of retinal arterioles were assessed by measuring changes in diameters of the vessels. In streptozotocin-induced diabetic rats and the age-matched controls, acetylcholine increased diameters of retinal arterioles in a dose-dependent manner. The vasodilator responses to acetylcholine in diabetic rats were smaller than those in control rats. The nitric oxide- and prostaglandin-independent vasodilation of retinal arterioles observed under treatment with combination of N(G)-nitro-l-arginine methyl ester (30 mg/kg, i.v.) and indomethacin (5 mg/kg, i.v.) were also attenuated by diabetes. Diabetes did not alter the dilator responses of retinal arterioles to sodium nitroprusside and forskolin. These results suggest that diabetes impairs EDHF-mediated vasodilation of retinal arterioles induced by acetylcholine. The impaired EDHF-mediated vasodilation may contribute to alteration of retinal hemodynamics in diabetes.
authors.affiliation: Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. nakaharat@pharm.kitasato-u.ac.jp
authors.forename: Taisuke
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Kaneko
authors.forename: Asami
authors.initials: A
authors.lastname: Mori
authors.forename: Maki
authors.initials: M
authors.lastname: Saito
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakahara
authors.forename: Kunio
authors.initials: K
authors.lastname: Ishii
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles; D001685:Biological Factors / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012171:Retinal Vessels / Q000187:drug effects* / Q000378:metabolism; D013311:Streptozocin; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D001685:Biological Factors; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D011453:Prostaglandins; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D013311:Streptozocin; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester