title: BMS-191011, an opener of large-conductance Ca2+-activated potassium channels, dilates rat retinal arterioles in vivo.
abstract: 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.
authors.affiliation: Department of Molecular Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Tokyo 108–8641, Japan.
authors.forename: Asami
authors.initials: A
authors.lastname: Mori
authors.forename: Sachi
authors.initials: S
authors.lastname: Suzuki
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: D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D008297:Male; D010069:Oxadiazoles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects*; D012161:Retinal Artery / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: C480883:3-((5-chloro-2-hydroxyphenyl)methyl)-5-(4-(trifluoromethyl)phenyl)-1,3,4-oxadiazol-2(3H)-one; D001562:Benzimidazoles; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010069:Oxadiazoles; D014665:Vasodilator Agents; C086491:NS 1619