Submitted on July 25, 2008
Revised on November 28, 2008
Accepted on December 19, 2008
Chronic hypoxia enhances 15-lipoxygenase mediated vasorelaxation in rabbit arteries
Nitin T Aggarwal1, Sandra L. Pfister1*, Kathryn M Gauthier1, Yuttana Chawengsub1, John E. Baker1, and William B. Campbell1
1 Medical College of Wisconsin
* To whom correspondence should be addressed. E-mail: spfister{at}mcw.edu.
15-Lipoxygenase (15-LO-1) metabolizes arachidonic acid (AA) to 11,12,15-trihydroxyeicosatrienoic acids (THETA) and 15-hydroxy-11,12-epoxyeicosatrienoic acids (HEETA) that dilate rabbit arteries. Increased endothelial 15-LO-1 expression enhances arterial relaxations to agonist. We tested the effect of hypoxia on 15-LO-1 expression, THETA and HEETA synthesis, and relaxations in the rabbit arteries. Incubation of rabbit aortic endothelial cells and isolated aortas in 0.7 % O2 increased 15-LO-1 expression. Rabbits were housed in a hypoxic atmosphere of 12 % O2 for 5 days. 15-LO-1 expression increased in the endothelium of the arteries of rabbits in 12% O2 compared to room air. THETA and HEETA synthesis was also enhanced in aortas and mesenteric arteries. AA hyperpolarized the smooth muscle cells in indomethacin and phenylepherine treated mesenteric arteries of hypoxic rabbits from -29.4 ± 1 mV to -50.1 ± 3 mV. The hyperpolarization to AA was less in arteries of normoxic rabbits (from -26.0 ± 2 mV to -37 ± 2 mV). This AA-induced hyperpolarization was inhibited by the 15-LO inhibitor BW755C. 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 to the normoxic rabbits (49.7 ± 6 % and 19.9 ± 2%, respectively). These relaxations were inhibited by BW755C 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.
