Vasodilation induced by oxygen/glucose deprivation is attenuated in cerebral arteries of SUR2 null mice

Adebowale Adebiyi, Elizabeth M. McNally, Jonathan H. Jaggar

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Physiological functions of arterial smooth muscle cell ATP-sensitive K + (K ATP) channels, which are composed of inwardly rectifying K + channel 6.1 and sulfonylurea receptor (SUR)-2 subunits, during metabolic inhibition are unresolved. In the present study, we used a genetic model to investigate the physiological functions of SUR2-containing K ATP channels in mediating vasodilation to hypoxia, oxygen and glucose deprivation (OGD) or metabolic inhibition, and functional recovery following these insults. Data indicate that SUR2B is the only SUR isoform expressed in murine cerebral artery smooth muscle cells. Pressurized SUR2 wild-type (SUR2 wt) and SUR2 null (SUR2 nl) mouse cerebral arteries developed similar levels of myogenic tone and dilated similarly to hypoxia (<10 mmHg PO2). In contrast, vasodilation induced by pinacidil, a K ATP channel opener, was ~71% smaller in SUR2 nl arteries. Human cerebral arteries also expressed SUR2B, developed myogenic tone, and dilated in response to hypoxia and pinacidil. OGD, oligomycin B (a mitochondrial ATP synthase blocker), and CCCP (a mitochondrial uncoupler) all induced vasodilations that were ~39-61% smaller in SUR2 nl than in SUR2 wt arteries. The restoration of oxygen and glucose following OGD or removal of oligomycin B and CCCP resulted in partial recovery of tone in both SUR2 wt and SUR2 nl cerebral arteries. However, SURnl arteries regained ~60- 82% more tone than did SUR2 wt arteries. These data indicate that SUR2-containing K ATP channels are functional molecular targets for OGD, but not hypoxic, vasodilation in cerebral arteries. In addition, OGD activation of SUR2-containing KATP channels may contribute to postischemic loss of myogenic tone.

Original languageEnglish (US)
Pages (from-to)H1360-H1368
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume301
Issue number4
DOIs
StatePublished - Oct 2011

Keywords

  • Adenosine 5'-triphosphate-sensitive potassium channels
  • Hypoxia
  • Ischemia
  • Mitochondria
  • Sulfonylurea receptors

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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