Reactive oxygen species mediate arachidonic acid-induced dilation in porcine coronary microvessels.
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 microm 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 microM) or diclofenac (10 microM) 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.
Oltman
Christine L
CL
Department of Internal Medicine and the Cardiovascular Research Center, University of Iowa and Department of Veterans Affairs Medical Center, Iowa City, 52246, USA. christine-oltman@uiowa.edu
Kane
Neal L
NL
Miller
Francis J
FJ
Spector
Arthur A
AA
Weintraub
Neal L
NL
Dellsperger
Kevin C
KC
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D003331:Coronary Vessels / Q000378:metabolism*; D005260:Female; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D008856:Microscopy, Fluorescence; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013552:Swine; D014316:Tritium; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D017382:Reactive Oxygen Species; D014316:Tritium; D015117:5,8,11,14-Eicosatetraynoic Acid; D016718:Arachidonic Acid