Chronic hypoxia enhances 15-lipoxygenase-mediated vasorelaxation in rabbit arteries
- 1 March 2009
- journal article
- retracted article
- Published by American Physiological Society in American Journal of Physiology-Heart and Circulatory Physiology
- Vol. 296 (3), H678-H688
- https://doi.org/10.1152/ajpheart.00777.2008
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% 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 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.This publication has 44 references indexed in Scilit:
- 15-Lipoxygenase metabolites contribute to age-related reduction in acetylcholine-induced hypotension in rabbitsAmerican Journal of Physiology-Heart and Circulatory Physiology, 2008
- Oxidant and Redox Signaling in Vascular Oxygen Sensing: Implications for Systemic and Pulmonary HypertensionAntioxidants and Redox Signaling, 2008
- Age-related decrease in 15-lipoxygenase contributes to reduced vasorelaxation in rabbit aortaAmerican Journal of Physiology-Heart and Circulatory Physiology, 2008
- Endothelial 15-Lipoxygenase-1 Overexpression Increases Acetylcholine-Induced Hypotension and Vasorelaxation in RabbitsHypertension, 2008
- S-acylation regulates Kv1.5 channel surface expressionAmerican Journal of Physiology-Cell Physiology, 2007
- The early effects of chronic hypoxia on the cardiovascular system in the rat: role of nitric oxideThe Journal of Physiology, 2006
- Effect of Body Warming on Regional Blood Flow Distribution in Conscious Hypoxic One-Month-Old RabbitsNeonatology, 2006
- Apamin-Sensitive K + Currents Mediate Arachidonic Acid-Induced Relaxations of Rabbit AortaHypertension, 2004
- Mammalian arachidonate 15-lipoxygenases: Structure, function, and biological implicationsProstaglandins & Other Lipid Mediators, 2002
- Vascular bed heterogeneity in age‐related endothelial dysfunction with respect to NO and eicosanoidsBritish Journal of Pharmacology, 2000