Interaction between nitric oxide and prostanoids in arterioles of rat cremaster muscle in vivo.
We studied in vivo interactions of nitric oxide (NO), oxidative stress, and prostanoids derived from the cyclooxygenase pathway in the arterioles studied by intravital microscopy in peripheral muscle. Topical administration of NO synthase (NOS) inhibitor Nomega-nitro-l-arginine (l-NNA) or cyclooxygenase inhibitor mefenamic acid (MA) alone leads to vasoconstriction. We found that l-NNA after MA induced an additional constriction, whereas MA after l-NNA induced a relative dilation. Therefore, an additional constriction was found when MA was administered after l-NNA in the presence of the thromboxane A2 synthase-PGH2 (TP) receptor antagonist SQ-29548. We also found a relative dilation when the TP receptor antagonist was administered after NOS inhibition by l-NNA. In the presence of superoxide dismutase and catalase, l-NNA-induced vasoconstriction is reduced, and the dilation observed after addition of MA in presence of the reactive oxygen species is no longer present. Taken together, these results showed that NO inhibition induced a shift in the synthesis or in the effects of cyclooxygenase products, in favor of constrictor prostanoids. This effect of NO inhibition disappears when reactive oxygen species are scavenged by superoxide dismutase and catalase.
Laboratoire d'Etude de la Microcirculation, Département de Biophysique, Hôpital F. Widal, 200 rue du Faubourg Saint-Denis, 75475 Paris Cedex 10, France.
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Laemmel
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Bonnardel-Phu
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Hou
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Seror
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Vicaut
D000818:Animals; D001160:Arterioles / Q000201:enzymology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002374:Catalase / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated; D025461:Feedback, Physiological / Q000502:physiology; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011453:Prostaglandins; D017482:Receptors, Thromboxane; D019335:Nitroarginine; D009569:Nitric Oxide; C045749:SQ 29548; D002374:Catalase; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D013482:Superoxide Dismutase