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Chronic hypoxia enhances 15-lipoxygenase-mediated vasorelaxation in rabbit arteries. Am J Physiol Heart Circ Physiol 2009 Mar;296(3):H678-88

Date

12/30/2008

Pubmed ID

19112096

Pubmed Central ID

PMC2660232

DOI

10.1152/ajpheart.00777.2008

Scopus ID

2-s2.0-64049085636   11 Citations

Abstract

15-Lipoxygenase (15-LO-1) metabolizes arachidonic acid (AA) to 11,12,15-trihydroxyeicosatrienoic acids (THETAs) and 15-hydroxy-11,12-epoxyeicosatrienoic acids (HEETA) that dilate rabbit arteries. Increased endothelial 15-LO-1 expression enhances arterial relaxations to agonists. We tested the effect of hypoxia on 15-LO-1 expression, THETA and HEETA synthesis, and relaxations in rabbit arteries. The incubation of rabbit aortic endothelial cells and isolated aortas in 0.7% O(2) increased 15-LO-1 expression. Rabbits were housed in a hypoxic atmosphere of 12% O(2) for 5 days. 15-LO-1 expression increased in the endothelium of the arteries of rabbits in 12% O(2) compared with room air. THETA and HEETA synthesis was also enhanced in aortas and mesenteric arteries. AA hyperpolarized the smooth muscle cells in indomethacin- and phenylephrine-treated mesenteric arteries of hypoxic rabbits from -29.4 +/- 1 to -50.1 +/- 3 mV. The hyperpolarization to AA was less in arteries of normoxic rabbits (from -26.0 +/- 2 to -37 +/- 2 mV). This AA-induced hyperpolarization was inhibited by the 15-LO inhibitor BW-755C. Nitric oxide and prostaglandin-independent maximum relaxations to acetylcholine (79.7 +/- 2%) and AA (38.3 +/- 4%) were enhanced in mesenteric arteries from hypoxic rabbits compared with the normoxic rabbits (49.7 +/- 6% and 19.9 +/- 2%, respectively). These relaxations were inhibited by BW-755C and nordihydroguaiaretic acid. Therefore, hypoxia increased the relaxations to agonists in the rabbit mesenteric arteries by enhancing endothelial 15-LO-1 expression and synthesis of the hyperpolarizing factors THETA and HEETA.

Author List

Aggarwal NT, Pfister SL, Gauthier KM, Chawengsub Y, Baker JE, Campbell WB

Authors

John E. Baker PhD Professor in the Surgery department at Medical College of Wisconsin
William B. Campbell PhD Chair, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Sandra L. Pfister PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

8,11,14-Eicosatrienoic Acid
Animals
Arachidonate 15-Lipoxygenase
Arachidonic Acid
Arteries
Biological Factors
Cyclooxygenase Inhibitors
Disease Models, Animal
Dose-Response Relationship, Drug
Endothelium, Vascular
Hypoxia
Lipoxygenase Inhibitors
Male
Membrane Potentials
Muscle, Smooth, Vascular
Nitric Oxide
RNA, Messenger
Rabbits
Time Factors
Tunica Intima
Vasoconstriction
Vasoconstrictor Agents
Vasodilation
Vasodilator Agents
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