Reactive oxygen species mediate arachidonic acid-induced dilation in porcine coronary microvessels

Christine L. Oltman, Neal L. Kane, Francis J. Miller, Arthur A. Spector, Neal L. Weintraub, Kevin C. Dellsperger

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Reactive oxygen species (ROS) have been proposed to mediate vasodilation in the microcirculation. We investigated the role of ROS in arachidonic acid (AA)-induced coronary microvascular dilation. Porcine epicardial coronary arterioles (110 ± 4 μm diameter) were mounted onto pipettes in oxygenated Krebs buffer. Vessels were incubated with vehicle or 1 mM Tiron (a nonselective ROS scavenger), 250 U/ml polyethylene-glycolated (PEG)-superoxide dismutase (SOD; an O2- scavenger), 250 U/ml PEG-catalase (a H2O2 scavenger), or the cyclooxygenase (COX) inhibitors indomethacin (10 μM) or diclofenac (10 μM) for 30 min. After endothelin constriction (30-60% of resting diameter), cumulative concentrations of AA (10-10-10-5 M) were added and internal diameters measured by video microscopy. AA (10-7 M) produced 37 ± 6% dilation, which was eliminated by the administration of indomethacin (4 ± 7%, P < 0.05) or diclofenac (-8 ± 8%, P < 0.05), as well as by Tiron (-4 ± 5%, P < 0.05), PEG-SOD (-10 ± 6%, P < 0.05), or PEG-catalase (1 ± 4%, P < 0.05). Incubation of small coronary arteries with [3H]AA resulted in the formation of prostaglandins, which was blocked by indomethacin. In separate studies in microvessels, AA induced concentration-dependent increases in fluorescence of the oxidant-sensitive probe dichlorodihydrofluorescein diacetate, which was inhibited by pretreatment with indomethacin or by SOD + catalase. We conclude that in porcine coronary microvessels, COX-derived ROS contribute to AA-induced vasodilation.

Original languageEnglish (US)
Pages (from-to)H2309-H2315
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume285
Issue number6 54-6
DOIs
StatePublished - Dec 2003
Externally publishedYes

Keywords

  • Coronary microcirculation
  • Cyclooxygenase

ASJC Scopus subject areas

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

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