Potassium channel activators protect the N-methyl-D-Aspartate-induced cerebral vascular dilation after combined hypoxia and ischemia in piglets

Abstract

Background and Purpose - 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. Methods - 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%)2 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 10-5mol/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. Results - 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