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Abstract

Contribution of K+ channels to arachidonic acid-induced endothelium-dependent vasodilation in rat isolated perfused mesenteric arteries.

A S Adeagbo and K U Malik
Journal of Pharmacology and Experimental Therapeutics August 1991, 258 (2) 452-458;
A S Adeagbo
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K U Malik
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Abstract

The contribution of K+ channels and cytochrome P450 generated arachidonic acid (AA) metabolites to the endothelium-dependent vasodilation produced by this fatty acid in the perfused rat isolated mesenteric arteries was examined using a variety of compounds known to inhibit transmembrane K+ channels and cytochrome P450 enzymes. AA (1-1000 nmol) caused dose- and endothelium-dependent vasodilation in the presence of indomethacin and the effect was neither altered by lipoxygenase (AA 861) nor cytochrome P450 monooxygenase (alpha-naphthoflavone, ketoconazole and metyrapone) inhibitors indicating that AA-induced, endothelium-dependent vasodilation in this vascular bed was not mediated by product(s) of AA metabolism. The vasodilator effect of AA was also not altered by L-NG-nitro-arginine, methylene blue (50 microM), oxyhemoglobin (5 microM) or superoxide dismutase (50 U/ml), thus ruling out nitric oxide being its mediator. Conversely, arterial perfusion with K(+)-free or excess (50 mM) K+ Krebs' solution, but not ouabain infusion, minimized the vasodilator effect of AA, suggesting that this action of the fatty acid is due to changes in membrane K+ conductance that is independent of Na+/K(+)-adenosine triphosphatase activity. The vasodilator action of BRL 34915 (a K+ channel activator) was also minimized by extracellular K+ depletion or excess K+ (50 mM), but not by ouabain. Apamin (0.5 microM) and crude scorpion venom (2.5 micrograms/ml) attenuated AA- but not BRL 34915-induced vasodilation. Glyburide (inhibitor of ATP-activated K+ channel) abolished the vasodilator action of AA and BRL 34915. Procaine, a nonspecific K+ channel blocker did not affect AA-induced vasodilation even though it attenuated that caused by BRL 34915.(ABSTRACT TRUNCATED AT 250 WORDS)

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Journal of Pharmacology and Experimental Therapeutics
Vol. 258, Issue 2
1 Aug 1991
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Abstract

Contribution of K+ channels to arachidonic acid-induced endothelium-dependent vasodilation in rat isolated perfused mesenteric arteries.

A S Adeagbo and K U Malik
Journal of Pharmacology and Experimental Therapeutics August 1, 1991, 258 (2) 452-458;

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Abstract

Contribution of K+ channels to arachidonic acid-induced endothelium-dependent vasodilation in rat isolated perfused mesenteric arteries.

A S Adeagbo and K U Malik
Journal of Pharmacology and Experimental Therapeutics August 1, 1991, 258 (2) 452-458;
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