Contribution of epoxyeicosatrienoic acids to the cerebral blood flow response to hypoxemia

Journal of Applied Physiology
Xiaoguang LiuRaymond C Koehler

Abstract

Adenosine A2A receptors and ATP-activated K(+) (KATP) channels contribute to part of the cerebral vasodilatory response to systemic hypoxia, but other mediators are likely involved. Epoxyeicosatrienoic acids (EETs) are cerebral vasodilators and are released from astrocytes exposed to hypoxia. Moreover, stimulation of metabotropic glutamate receptors (mGluR) produces vasodilation by an EET-dependent mechanism. Here, we tested the hypothesis that EET signaling and mGluR activation contribute to hypoxic vasodilation. Laser-Doppler flow was measured over cerebral cortex of anesthetized rats subjected to stepwise reductions in arterial oxygen saturation to 50-70%. Hypoxic reactivity was calculated as the slope of the change in laser-Doppler flow vs. the reciprocal of arterial oxygen content. Hypoxic reactivity significantly decreased from 9.2 ± 1.9 (±95% confidence interval) in controls with vehicle treatment to 2.6 ± 1.4 with the EET antagonist 14,15-epoxyeicosa-5(Z)-enoic acid, to 3.0 ± 1.5 with the EET synthesis inhibitor MS-PPOH, to 1.9 ± 2.3 with the combined mGluR subtype 1 and 5 antagonists 2-methyl-6-(phenylethynyl)pyridine and LY367385, to 5.6 ± 1.2 with the KATP channel inhibitor glibenclamide, and to 5.8 ± 2.3 with the A2...Continue Reading

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Citations

Aug 30, 2014·Journal of Physiology, Paris·R Moraga-AmaroJ Stehberg
Dec 18, 2015·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Ryan L HoilandPhilip N Ainslie
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Jan 16, 2019·Journal of Molecular Neuroscience : MN·Qiong WuQuanzhong Chang
Feb 27, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·William M ChilianVahagn Ohanyan

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