title: Pharmacological evidence for the presence of functional beta(3)-adrenoceptors in rat retinal blood vessels.
abstract: The aim of this study was to examine whether stimulation of beta(3)-adrenoceptors dilates rat retinal blood vessels and how diabetes affects the vasodilator responses. Images of ocular fundus were captured with an original high-resolution digital fundus camera in vivo. The retinal vascular responses were evaluated by measuring diameter of retinal blood vessels contained in the digital images. Both systemic blood pressure and heart rate (HR) were continuously recorded. The beta(3)-adrenoceptor agonist CL316243 (0.3-10 microg/kg/min, i.v.) increased diameter of retinal arterioles (at 10 microg/kg/min, a 31% increase) and decreased mean blood pressure (at 10 microg/kg/min, a 21% decrease) in a dose-dependent manner. CL316243 produced a small but significant increase in HR (at 10 microg/kg/min, a 9% increase). Both SR59230A (1 mg/kg, i.v.) and L-748337 (50 microg/kg, i.v.), beta(3)-adrenoceptor antagonists, significantly prevented CL316243-induced retinal vasodilator responses. Similar observations were made with another beta(3)-adrenoceptor agonist, BRL37344. The beta(2)-adrenoceptor agonist salbutamol also increased diameter of retinal arterioles (at 10 microg/kg/min, a 43% increase), whereas the drug produced greater decrease in blood pressure (at 10 microg/kg/min, a 46% decrease) and increase in HR (at 10 microg/kg/min, a 16% increase), compared with beta(3)-adrenoceptor agonists. The retinal vasodilator responses to CL316243 and BRL37344 observed under blockade of beta(1)/beta(2)-adrenoceptors with propranolol (2 mg/kg, i.v. bolus followed by 100 microg/kg/min infusion) were unaffected 2 weeks after induction of diabetes by the combination of streptozotocin treatment and D: -glucose feeding. On the other hand, the vasodilator responses to salbutamol of retinal arterioles were significantly reduced in diabetic rats. These results suggest that stimulation of beta(3)-adrenoceptors causes the vasodilation of retinal arterioles in vivo and the vasodilator responses are unaffected at the early stage of diabetes.
authors.affiliation: Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
authors.forename: Asami
authors.initials: A
authors.lastname: Mori
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Miwa
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: D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use; D058673:Adrenergic beta-3 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000517:prevention & control; D004149:Dioxoles / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000494:pharmacology / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051381:Rats; D012171:Retinal Vessels / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D058673:Adrenergic beta-3 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D004149:Dioxoles; D004983:Ethanolamines; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; C057368:BRL 37344