BMS-191011, an opener of large-conductance Ca2+-activated potassium channels, dilates rat retinal arterioles in vivo

The large-conductance CA(2+)-activated K(+) (BK(CA)) channels modulate vascular smooth muscle tone but the role of BK(CA) channels in regulation of retinal circulation remains unclear. In the present study, we examined the effects of BMS-191011 and NS 1619, openers of BK(CA) channels, on rat retinal blood vessels in vivo. Male Wistar rats (8- to 10-week-old) were anesthetized with pentobarbital sodium (50 mg/kg, intraperitoneally (i.p.)) and treated with tetrodotoxin (50 µg/kg, intravenously (i.v.)) to eliminate any nerve activity and prevent movement of the eye under artificial ventilation. A mixture solution of adrenaline and noradrenaline (9:1) was infused to maintain adequate systemic circulation. BMS-191011 (10-100 µg/kg, i.v.) and NS 1619 (0.1-1.0 µg/kg, i.v.) increased the diameter of retinal arterioles without altering systemic blood pressure and heart rate significantly. The vasodilator responses to BMS-191011, but not to NS 1619, were significantly diminished by intravitreal injection of iberiotoxin (an inhibitor of BK(CA) channels, 20 pmol/eye). These results suggest that BMS-191011 dilates rat retinal arterioles through activation of iberiotoxin-sensitive BK(CA) channels in vivo. The BK(CA) channel opener could be considered as a candidate for improving retinal circulation without severe cardiovascular side-effects.