Pharmacological evidence for the presence of functional β3-adrenoceptors in rat retinal blood vessels

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 mu g/kg/min, i.v.) increased diameter of retinal arterioles (at 10 mu g/kg/min, a 31% increase) and decreased mean blood pressure (at 10 mu g/kg/min, a 21% decrease) in a dose-dependent manner. CL316243 produced a small but significant increase in HR (at 10 mu g/kg/min, a 9% increase). Both SR59230A (1 mg/kg, i.v.) and L-748337 (50 mu g/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 mu g/kg/min, a 43% increase), whereas the drug produced greater decrease in blood pressure (at 10 mu g/kg/min, a 46% decrease) and increase in HR (at 10 mu g/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 mu g/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.