Involvement of Gi protein-dependent BK channel activation in β-adrenoceptor-mediated dilation of retinal arterioles in rats.

Circulating catecholamines contribute to the regulation of retinal vascular tone. Our previous studies have demonstrated that the activation of large-conductance Ca-activated K (BK) channels is involved in the β-adrenoceptor-mediated dilation of retinal arterioles in rats. The present study aimed to examine the role of Gi protein in the β-adrenoceptor-mediated activation of BK channels in the retinal arterioles. Images of in vivo rat ocular fundi were captured, and the diameters of retinal arterioles were measured. Systemic blood pressure and heart rate were recorded continuously. Intravenous infusion of formoterol (0.01-0.3 μg/kg/min), a β-adrenoceptor agonist, increased the diameter of retinal arterioles but decreased mean arterial pressure in a dose-dependent manner. Intravitreal injection of iberiotoxin (20 pmol/eye), an inhibitor of BK channels, significantly attenuated the formoterol-induced dilation of retinal arterioles. Similar results were obtained when salbutamol (0.03-3 μg/kg/min), another β-adrenoceptor agonist, was used instead of formoterol. However, iberiotoxin had no significant effect on retinal vasodilator responses to intravenous infusion of denopamine (1-30 μg/kg/min; a β-adrenoceptor agonist), CL316243 (0.3-10 μg/kg/min; a β-adrenoceptor agonist), prostaglandin I (0.03-10 μg/kg/min; a prostanoid IP receptor agonist), and forskolin (1-10 μg/kg/min; an adenylyl cyclase activator). Intravitreal injection of pertussis toxin (66 ng/eye; a Gi protein inhibitor) significantly attenuated the dilation of retinal arterioles induced by formoterol but not by denopamine and CL316243. In the presence of pertussis toxin, iberiotoxin had no inhibitory effect on formoterol-induced dilation of retinal arterioles. These results suggest that stimulation of β-adrenoceptors dilates retinal arterioles through pertussis toxin-sensitive Gi protein-dependent activation of BK channels in rats in vivo.