engleski

The effects of hyperbaric oxygenation on cerebral vascular function of diabetic rats

Untreated diabetes mellitus leads to many vascular complications, e.g. microangiopaty and macroangiopaty, while diabetic patients have higher risks of developing stroke. Inhibition of 20-HETE and/or increasing of epoxyeicosatrienoic acids (EETs) levels may decrease cerebral damage following stroke. Hyperbaric oxygenation (HBOT) is widely used clinical treatment for various ischemic injuries but is still experimental in treatment of stroke. Underlying cellular and molecular mechanisms of HBOT by affecting vascular function are still not known completely. Our recent studies in diabetic rats showed significantly reduced dilation of cerebral resistance vessels in response to reduced pO2 and ACh, which is restored with HBOT, possibly mediated by effect of CYP450-epoxygenases’ vasodilating metabolites 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 HBOT, and increased protein expression of CYP4A1, CYP4A2 and CYP4A3. The latest two share 97% homology, and both are known to catalyze arachidonic acid-hydroxylation and 11, 12-epoxidation thus promoting not only vasoconstriction, but also vasodilation. Taken all together, these results demonstrate that HBOT promotes protection of vascular function by changing mRNA and protein expression, and subsequently, restoring dilation of cerebral vessels, thus improving cerebrovascular function and tissue perfusion in diabetes mellitus by affecting several enzymatic pathways, most prominently CYP450 hydroxylases and epoxygenases.

hyperbaric oxygenation; cerebral vasular function; diabetes

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