Responses of cerebral arterioles in diabetic rats to activation of ATP- sensitive potassium channels

The goal of this study was to determine whether responses of pial arterioles to activation of ATP-sensitive potassium channels are altered during diabetes mellitus. We measured changes in diameter of pial arterioles in vivo in nondiabetic and diabetic rats (streptozotocin; 50-60 mg/kg ip; studied 3-4 mo after streptozotocin) in response to RP52891, an activator of ATP-sensitive potassium channels. RP52891 (1.0 μM) dilated pial arterioles in nondiabetic rats by 16 ± 1% but constricted pial arterioles in diabetic rats by 2 ± 2% (means ± SE; P < 0.05 vs. response in nondiabetic rats). Dilatation of pial arterioles in nondiabetic rats in response to RP52891 was inhibited by glibenclamide (1.0 μM) but was not altered by N(G)-monomethyl- L-arginine (1.0 μM), apamin (0.1 μM), or charybdotoxin (50 nM). Thus dilatation of pial arterioles in response to RP52891 appears to be due to activation of ATP-sensitive potassium channels and does not involve nitric oxide or calcium-activated potassium channels. To determine whether impaired dilatation of pial arterioles in response to RP52891 in diabetic rats was related to a nonspecific effect of diabetes mellitus on vasodilatation, we measured diameter of pial arterioles in nondiabetic and diabetic rats in response to nitroglycerin. Nitroglycerin (1.0 μM) dilated pial arterioles by 12 ± 1% in nondiabetic rats and 16 ± 2% in diabetic rats (P > 0.05). Thus impaired dilatation of pial arterioles in diabetic rats in response to RP52891 also is not related to a nonspecific effect of diabetes mellitus on vasodilatation. The findings of the present study suggest that ATP-sensitive potassium channels are functional in cerebral arterioles in vivo and are impaired during diabetes mellitus.