Dimethylsulfoxide and ethanol, commonly used diluents, prevent dilation ofpial arterioles by openers of K-ATP ion channels

Ethanol and dimethylsulfoxide are commonly used as diluents for water-insol uble drugs. Both are antioxidants. An earlier study of cats presented pharm acological evidence indicating that oxidants could open the K-ATP ion chann el in cerebral surface arterioles [pial arterioles] and that antioxidants i ncluding dimethylsulfoxide and L-Cysteine prevented opening of these channe ls. Ethanol was not tested. The present study extends the older observation s to a second species, the rat, and examines ethanol as well as dimethylsul foxide and L-cysteine. A microscope and image splitter were used to measure arteriolar diameters under a closed cranial window in pentobarbitalanesthe tized, paralyzed rats. Drugs were topically applied. Dose-dependent dilatio ns produced by two well-established openers of the K-ATP ion channel were i nhibited in dose-dependent manner by ethanol at doses from 0.01% to 0.075%. Above this dose, the effect disappeared, Dilation by sodium nitroprusside was not affected. Dimethylsulfoxide and L-Cysteine inhibited dilation produ ced by pinacidil, Dimethylsulfoxide inhibited pinacidil in a dose-dependent manner at doses from 0.01% to 0.2%. L-Cysteine inhibited pinacidil. Since all the inhibitory drugs have antioxidant properties, their effect may be a reflection of that property as suggested in an earlier paper. Ethanol and dimethylsulfoxide inhibited in doses frequently present when these agents a re used as solvents. When investigators use these solvents to dissolve wate r-insoluble, topically applied drugs, we suggest that they first test the p ossibility that their observations are being made under conditions in which opening of the K-ATP ion channel is inhibited. (C) 2001 Elsevier Science B .V. All rights reserved.