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BMS-191011, an Opener of Large-Conductance Ca2+-activated Potassium Channels, Dilates Rat Retinal Arterioles in Vivo

BMS-191011, an Opener of Large-Conductance Ca2+-activated Potassium Channels, Dilates Rat Retinal Arterioles in Vivo

Asami Mori, Sachi Suzuki, Kenji Sakamoto, Tsutomu Nakahara, Kunio Ishii

Biol Pharm Bull. 2011;34(1):150-2.

PMID: 21212534

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP202821816	BMS-191011		202821-81-6	Price

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