Potassium Channel Activators (PCA) protect NMDA-induced cerebral arteriolar dilation after Hypoxia/Ischemia(H/I)

R. Veltkamp, F. Domoki, F. Bari, T. M. Louis, D. W. Busija

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Abstract

Cerebral arteriolar dilation to N-methyl-D-aspartate (NMDA), a neuronally mediated process, is sensitive to H/I. We examined whether pretreatment with the PCA NS1619 or aprikalim preserves vascular responses to NMDA after H/I. Methods: Pial arteriolar diameters were measured in piglets using a closed cranial window and intravital microscopy. Arteriolar responses to NMDA were recorded before and 1 hour after 10 min of hypoxia plus 10 min of ischemia induced by increasing intracranial pressure. Results: Arteriolar responses to NMDA were significantly attenuated after H/I. Baseline compared to post-H/I diameters were 9±4% vs. 3±2% at 10-5M, 22±4% vs. 4±2% at 5×10-5M, and 33±4% vs. 7±2% at 10-4M (mean±SEM; p<0.05, n=7). Pretreatment with NS1619 or aprikalim preserved arteriolar responses to NMDA after H/I. For NS1619 (10-5M; n=6): 9±2% vs. 6±4% at 10-5M, 19±6% vs 21±5% at 5×10-5M, 35±3% vs. 31±5% at 10-4M. For aprikalim (10-6M; n=7): 6±2% vs. 8±2% at 10-5M, 22±6% vs. 15±3% at 5×10-5M, 41±5% vs. 32±6% at 10-4M. Other vasodilating agents did not preserve responses to NMDA despite causing similar dilation as PCA. Conclusion: These findings suggest a neuroprotective effect of PCA by action on neurons rather than by vasodilation.

Original languageEnglish
Pages (from-to)A953
JournalFASEB Journal
Volume12
Issue number5
Publication statusPublished - Mar 20 1998

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ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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