Arachidonic acid-induced vasodilation of rat small mesenteric arteries is lipoxygenase-dependent

Allison W. Miller, Prasad V G Katakam, Hon chi Lee, Christina D. Tulbert, David W. Busija, Neal Lee Weintraub

Research output: Contribution to journalArticle

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Abstract

We examined the mechanism of arachidonic acid-induced vasodilation in rat small mesenteric arteries and determined the primary arachidonic acid metabolites produced by these arteries. Responses to arachidonic acid in small mesenteric arteries from Sprague-Dawley rats were investigated in vitro in the presence or absence of endothelium or after pretreatment with inhibitors of nitric oxide (NO), cyclooxygenase, cytochrome P450, lipoxygenase, or K+ channels. In addition, the metabolism of arachidonic acid was examined by incubating arteries with [3H]arachidonic acid in the presence and absence of cyclooxygenase, cytochrome P450, or lipoxygenase inhibitors. Finally, the vascular response to both 12(S)-hydroxyeicosatetraenoic acid (HETE) and 12(S)-hydroperoxyeicosatetraenoic acid (HPETE) was determined. Arachidonic acid induced an endothelium-dependent vasodilation that was abolished by lipoxygenase inhibitors [cin-namyl-3,4-dihydroxy-cyanocinnamate (CDC) or 5,8,11-eicosatriynoic acid (ETI)] and KCI, whereas it was partially inhibited by either tetraethylammonium or iberiotoxin. In contrast, neither NO nor cytochrome P450 enzyme inhibitors affected arachidonic acid-mediated dilation, whereas inhibition of cyclooxygenase enhanced dilation. Biochemical analysis revealed that small mesenteric arteries primarily produce 12-HETE, a lipoxygenase metabolite. Moreover, CDC and ETI inhibited the production of 12-HETE. Finally, both 12(S)-HETE and 12(S)-HPETE induced a concentration-dependent vasodilation in mesenteric arteries. These findings provide functional and biochemical evidence that the lipoxygenase pathway mediates arachidonic acid-induced vasodilation in rat small mesenteric arteries through a K+ channel-dependent mechanism.

Original languageEnglish (US)
Pages (from-to)139-144
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume304
Issue number1
DOIs
StatePublished - Jan 1 2003
Externally publishedYes

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Mesenteric Arteries
Lipoxygenase
Arachidonic Acid
Vasodilation
Prostaglandin-Endoperoxide Synthases
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
Cytochrome P-450 Enzyme System
Hydroxyeicosatetraenoic Acids
Lipoxygenase Inhibitors
Endothelium
Dilatation
Nitric Oxide
Arteries
Acids
Tetraethylammonium
Blood Vessels
Sprague Dawley Rats

ASJC Scopus subject areas

  • Pharmacology

Cite this

Arachidonic acid-induced vasodilation of rat small mesenteric arteries is lipoxygenase-dependent. / Miller, Allison W.; Katakam, Prasad V G; Lee, Hon chi; Tulbert, Christina D.; Busija, David W.; Weintraub, Neal Lee.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 304, No. 1, 01.01.2003, p. 139-144.

Research output: Contribution to journalArticle

Miller, Allison W. ; Katakam, Prasad V G ; Lee, Hon chi ; Tulbert, Christina D. ; Busija, David W. ; Weintraub, Neal Lee. / Arachidonic acid-induced vasodilation of rat small mesenteric arteries is lipoxygenase-dependent. In: Journal of Pharmacology and Experimental Therapeutics. 2003 ; Vol. 304, No. 1. pp. 139-144.
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