Contractile responses of isolated rat mesenteric arteries to acute episodes of severe hypoxia and subsequent reoxygenation

Jason Bruce, Michael Taggart, Clare Austin

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

This study further investigates the mechanisms responsible for the effects of acute and severe hypoxia, and subsequent reoxygenation, on the contractility of isolated rat mesenteric arteries. In noradrenaline (NA)-contracted arteries, hypoxia caused a relaxation to near baseline levels. Reoxygenation resulted in an immediate transient contraction before tension returned more slowly to prehypoxia levels. Similar responses to hypoxia were observed in tissues precontracted by addition of KCl (60 mM) or U46619 (10 microM); however, the transient contraction upon reoxygenation was absent (KCl) or reduced (U46619). Responses to hypoxia were independent of changes in intracellular calcium ([Ca2+]i), while those to reoxygenation were accompanied by corresponding changes in [Ca2+]i and were completely abolished by ryanodine. In NA-contracted tissues, all responses were unaffected by endothelial removal or by inhibitors of nitric oxide synthase and cyclooxygenase. The K+ channel blockers triethylamine (TEA), glibenclamide, and 4-aminopyridine (4-AP) had no effect on the responses to hypoxia. The transient contractile response to reoxygenation was, however, significantly reduced in the presence of 4-AP. The response to reoxygenation, but not that to hypoxia, was inhibited by the antioxidant dithiothreitol (DTT) and the NAD(P)H-oxidase inhibitor diphenyliodonium (DPI). These data suggest that hypoxic vasodilation occurs independently of reductions in [Ca2+]i. Alternatively, transient contractions on reoxygenation are dependent upon the generation of reactive oxygen species and the release of stored Ca2+.

Original languageEnglish
Pages (from-to)303-12
Number of pages10
JournalMicrovascular Research
Volume68
Issue number3
DOIs
Publication statusPublished - 30 Nov 2004

Keywords

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/pharmacology
  • 4-Aminopyridine/pharmacology
  • Adenosine Triphosphate/chemistry
  • Animals
  • Anti-Arrhythmia Agents/pharmacology
  • Calcium/metabolism
  • Endothelium, Vascular/metabolism
  • Ethylamines/pharmacology
  • Glyburide/pharmacology
  • Hypoxia
  • Male
  • Mesenteric Arteries/drug effects
  • Muscle Contraction
  • Norepinephrine/pharmacology
  • Oxygen/metabolism
  • Potassium/chemistry
  • Potassium Channel Blockers/pharmacology
  • Potassium Channels/chemistry
  • Rats
  • Rats, Wistar
  • Reperfusion Injury
  • Ryanodine/pharmacology

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