engleski

Hyperbaric oxygenation - the role of EETs

Hyperbaric oxygenation (HBO2) is widely used clinical treatment for various ischemic injuries. Recently, cellular and molecular mechanisms of HBO2 affecting vascular function are being extensively studied. For example, inhibition of 20-HETE and/or increasing of epoxyeicosatrioneic acids (EETs) levels may decrease cerebral damage following stroke, while levels of these mediators may be modified by HBO2. Our recent studies in rat healthy conductive vessels suggest the role for EETs in modulating relaxation response to ANG-(1- 7) with HBO2 that is mediated via potassium channels other than KATP channels. HBO2 increased the responses to ANG-(1- 7). Furthermore, our studies in diabetic rats showed significantly reduced dilation of cerebral resistance vessels in response to reduced pO2 and ACh, which is restored with HBO2, possibly mediated by effect of CYP450- epoxygenases' vasodilating metabolites of EETs on KATP channels. In addition, our data on mRNA expression showed up-regulation of CYP4A3 and CYP450-epoxygenase genes in cerebral blood vessels in diabetic rats treated with HBO2, and increased protein expression of CYP4A1, CYP4A2 and CYP4A3. The latest two share 97%homology, and both are known to catalyze arachidonic acid ω-hydroxylation and 11, 12-epoxidation thus promoting not only vasoconstriction, but also vasodilation. taken all together, these results demonstrate that HBO2 promotes protection of vascular function in macro- and microcirculation by changeing mRNA and protein expression, and subsequently, restoring dilation responses of vessels in various beds. This improves vessels' function and tissue perfusion by affecting several enzymatic pathways, most prominently CYP450 hydoxylases and epoxygenases, both in healthy and diabetic circulation.

hyperbaric oxigenation; vascular function; EETs

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