Global ischemia impairs ATP-sensitive K+ channel function in cerebral arterioles in piglets

Ferenc Bari, Thomas M. Louis, Wei Meng, David W. Busija

Research output: Article

75 Citations (Scopus)

Abstract

Background and Purpose: Indirect evidence from studies in which calcitonin gene-related peptide was used indicates that anoxic stress suppresses functioning of cerebral vascular ATP-sensitive K+ channels. The purpose of this study was to directly examine effects of total global ischemia on cerebral arteriolar dilator responses to activators of ATP- sensitive K+ channels. Methods: We measured pial arteriolar diameters in anesthetized piglets using a closed cranial window and intravital microscopy. Baseline diameters were approximately 100 μm. Arteriolar responses to aprikalim (10-8 and 10-6 mol/L), a pharmacological activator of ATP- sensitive K+ channels, and iloprost (0.1 and 1 μg/mL), a physiological activator of these channels, were determined before and 1, 2, and 4 hours after a 10-minute period of total global ischemia. Ischemia was caused by increasing intracranial pressure. Results: Before ischemia, aprikalim dilated cerebral arterioles by 7±2% at 10-8 mol/L and by 25±4% at 10-6 mol/L (n=5). At 1 hour after ischemia, aprikalim did not cause significant dilation at either dose (3±2% at 10-8 mol/L and 7±4% at 10-6 mol/L: P<.05 compared with corresponding preischemic response). Arteriolar dilation returned toward normal values at 2 and 4 hours. Similar results were found with iloprost. Furthermore, prior treatment with indomethacin (5 mg/kg) preserved normal arteriolar dilation to aprikalim and iloprost after ischemia. In contrast, arteriolar dilator responses to prostaglandin E2 were intact after ischemia. Conclusions: Ischemia transiently eliminates cerebral arteriolar dilation to activation of ATP-sensitive K+ channels; arteriolar responses are suppressed at 1 hour and return toward normal over 2 to 4 hours. In addition, reduced responsiveness can be prevented by prior treatment with indomethacin.

Original languageEnglish
Pages (from-to)1874-1881
Number of pages8
JournalStroke
Volume27
Issue number10
DOIs
Publication statusPublished - okt. 1996

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing

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