Our previous studies indicate that function of ATP-dependent K+ channels (K(ATP)) in cerebral arterioles is suppressed after ischemia. In the current study, we examined pial arteriolar responses to forskolin, dibutyryl-cAMP, NS-1619, and methionine (met)-enkephalin, activators of calcium-dependent K+ channels (K(Ca)) before and 1 hour after 10 minutes of total, global ischemia in anesthetized piglets. Arteriolar diameters were measured using a closed cranial window and intravital microscopy. All pharmacologic agents were given topically. Baseline diameters were approximately 100 microm, and diameters had returned to normal by 1 hour after ischemia. Forskolin dilated arterioles by 9 +/- 3%, 18 +/- 4%, and 31 +/- 12% at 5 x 10(-8), 5 x 10(-7), and 10(-6) mol/L, respectively (P < 0.05, n = 10). In addition, dibutyryl-cAMP dilated arterioles by 8 +/- 2% at 10(-4) mol/L and 14 +/- 2% at 3 x 10(-4) mol/L (P < 0.05, n = 6). Also, NS-1619 increased diameter of arterioles by 9 +/- 2% at 10(-7) mol/L and 17 +/- 9% at 10(-5) mol/L (P < 0.05, n = 5). Finally, met-enkephalin dilated arterioles by 9 +/- 2% at 10(-8) mol/L and 16 +/- 3% at 10(-6) mol/L (P < 0.05, n = 5). At 1 hour after ischemia, arteriolar dilator effects to forskolin, dibutyryl-cAMP and NS-1619, and met-enkephalin were intact. Thus, in contrast to K(ATP), K(Ca) in cerebral arterioles are resistant to ischemic stress.