['Cerebral arteriolar dilation to N-methyl-D-aspartate (NMDA) is a neuronally mediated multistep process that is sensitive to cerebral hypoxia and ischemia (H/I). We tested the hypothesis that topical pretreatment with the selective potassium channel agonists NS1619 and aprikalim preserves the vascular response to NMDA after consecutive H/I.', 'Pial arteriolar diameters were measured in anesthetized piglets with the use of a closed cranial window and intravital microscopy. Arteriolar responses to NMDA (10(-5), 5 x 10(-5), and 10(-4) mol/L) were recorded before and 1 hour after 10 minutes of hypoxia (8.5% O2 in N2) plus 10 minutes of ischemia (H/I). Ischemia was induced by increasing intracranial pressure. Subgroups were topically pretreated with 10(-5) mol/L NS1619, 10(-6) mol/L aprikalim, 10(-6) mol/L calcitonin gene-related peptide (CGRP), or 10(-5) mol/L papaverine. We also examined the effects of H/I on vascular responses to kainate (10(-4) mol/L) to assess specificity of neuronal injury.', 'Arteriolar responses to NMDA were significantly attenuated after H/I. Baseline compared with post-H/I arteriolar diameters were 9+/-4% versus 3+/-2% at 10(-5) mol/L, 22+/-4% versus 4+/-2% at 5 x 10(-5) mol/L, and 33+/-4% versus 7+/-2% at 10(-4) mol/L (mean+/-SE; all P<.05, n=7). Pretreatment with NS1619 and aprikalim preserved the arteriolar responses to NMDA after H/I. For NS1619 (n=6), values were as follows: 9+/-2% versus 6+/-4% at 10(-5) mol/L, 19+/-6% versus 21+/-5% at 5 x 10(-5) mol/L, and 35+/-3% versus 31+/-5% at 10(-4) mol/L. For aprikalim (n=7), values were as follows: 6+/-2% versus 8+/-2% at 10(-5) mol/L, 22+/-6% versus 15+/-3% at 5 x 10(-5) mol/L, and 41+/-5% versus 32+/-6% at 10(-4) mol/L. In contrast, piglets pretreated with CGRP (n=6) or papaverine (n=5) showed no preservation of the vascular response to NMDA after H/I, although these compounds dilated the arterioles to an extent similar to that with NS1619/aprikalim. Kainate-induced arteriolar dilation (n=6) was largely preserved after H/I compared with preischemic responses.'] Do potassium channel activators protect the N-methyl-D-aspartate-induced cerebral vascular dilation after combined hypoxia and ischemia in piglets?