Dimethylsulfoxide and ethanol, commonly used diluents, prevent dilation of pial arterioles by openers of KATP ion channels ☆

Ethanol and dimethylsulfoxide are commonly used as diluents for water-insoluble drugs. Both are antioxidants. An earlier study of cats presented pharmacological evidence indicating that oxidants could open the KATP ion channel in cerebral surface arterioles [pial arterioles] and that antioxidants including dimethylsulfoxide and l-cysteine prevented opening of these channels. Ethanol was not tested. The present study extends the older observations to a second species, the rat, and examines ethanol as well as dimethylsulfoxide and l-cysteine. A microscope and image splitter were used to measure arteriolar diameters under a closed cranial window in pentobarbital-anesthetized, paralyzed rats. Drugs were topically applied. Dose-dependent dilations produced by two well-established openers of the KATP ion channel were inhibited 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 produced 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 are used as solvents. When investigators use these solvents to dissolve water-insoluble, topically applied drugs, we suggest that they first test the possibility that their observations are being made under conditions in which opening of the KATP ion channel is inhibited.