This study was designed to characterize the role of ATP sensitive (K(ATP)) and calcium sensitive (K(ca)) K(+) channel activation in N-methyl-d-aspartate (NMDA)-induced pial artery dilation in newborn pigs equipped with a closed cranial window. NMDA (10(-8), 10(-6)M) elicited pial artery dilation that was blunted by the K(ATP) channel antagonist glibenclamide (10(-6)M) and attenuated by the K(ca) channel antagonist iberiotoxin (10(-7)M) (8 +/- 1% and 14 +/- 1% versus 2 +/- 1% and 4 +/- 1% versus 5 +/- 1% and 9 +/- 2% for NMDA in the absence and presence of glibenclamide or iberiotoxin, respectively). Combined administration of glibenclamide and iberiotoxin essentially eliminated the response. Similar results were observed for glutamate. These data show that NMDA elicits cerebrovasodilation through activation of K(ATP) and K(ca) channels in newborn pigs.