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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:78.)
© 2006 American Heart Association, Inc.

Vascular Biology

Reticulocyte 15-Lipoxygenase-I Is Important in Acetylcholine-Induced Endothelium-Dependent Vasorelaxation in Rabbit Aorta

Xin Tang; Blythe B. Holmes; Kasem Nithipatikom; Cecilia J. Hillard; Hartmut Kuhn; William B. Campbell

From the Department of Pharmacology and Toxicology (X.T., B.B.H., K.N., C.J.H., W.B.C.), Medical College of Wisconsin, Milwaukee; and the Institute of Biochemistry (H.K.), University Medicine Berlin–Charité, Berlin, Germany.

Correspondence to William B. Campbell, Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226. E-mail wbcamp{at}mcw.edu

Objective— Aortic 15-lipoxygenase (15-LO) metabolizes arachidonic acid (AA) to 15-hydroperoxyeicosatetraenoic acid, which is then converted to the vasodilators 15-hydroxy-11,12-epoxyeicosatrienoic acid and 11,12,15-trihydroxyeicosatrienoic acid. These metabolites contribute to endothelium-dependent relaxations of rabbit aorta to AA and acetylcholine. We investigated the identity of rabbit aortic 15-LO and studied its importance in the regulation of vascular tone.

Methods and Results— RT-PCR using 12-lipoxygenase/15-LO specific primers resulted in a 572-bp product with a sequence identical to 15-LO-I from rabbit aorta. A RT-PCR/restriction digest strategy excluded expression of 12-lipoxygenase. Immunoblotting revealed 15-LO-I expression in rabbit endothelial and smooth muscle cells. Aortic homogenates and cytosolic fractions metabolize AA to 15(S)-hydroxyeicosatetraenoic acid and linoleic acid to 13(S)-hydroxyoctadecadienoic acid. This activity was blocked by LO inhibitors. The kinetic characteristics (Michaelis constant of aortic 15-LO is 2.2±0.3 µmol/L for AA and 23.5±3.3 µmol/L for linoleic acid) of aortic 15-LO were similar to those of the purified 15-LO-I. An antisense oligonucleotide inhibited 15-LO-I expression in rabbit aorta. Indomethacin and nitro-L-arginine-resistant relaxations to acetylcholine were inhibited by 15-LO-I antisense oligonucleotide but not by the scrambled oligonucleotide.

Conclusions— 15-LO-I is expressed in rabbit aortic endothelium and is important in endothelium-dependent regulation of vascular tone.

15-LO-I is expressed in rabbit aorta. 15-LO regulates vasodilatory eicosanoid synthesis and vascular tone.

Key Words: endothelium • arachidonic acid • 15-lipoxygenase • endothelium-derived hyperpolarizing factor

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