engleski

Hyperbaric oxygenation affects the mechanisms of acetylcholine-induced relaxation in diabetic rats

The effects of hyperbaric oxygenation (HBO2) on acetylcholine-induced vasorelaxation (AChIR) were evaluated in male Sprague-Dawley (SD) rats randomized into four groups:healthy controls (Ctrl), diabetic rats (DM), and control and diabetic rats that underwent hyperbaric oxygenation (Ctrl+HBO2 and DM+HBO2). AChIR was measured in aortic rings, with L- NAME, indomethacin, or MS-PPOH and a combination of inhibitors. mRNA expression of eNOS, iNOS, COX1 and COX2 was assessed by qPCR, and protein expression of CYP4A(1-3) by Western blot. Plasma antioxidative capacity and systemic oxidative stress were determined with the Ferric reducing ability of plasma (FRAP) and thiobarbituric acid-reactive substances (TBARS) assays, respectively. AChIR was preserved in all groups of rats, but mediated with different mechanisms.In all experimental groups of rats, AChIR was mediated mainly by NO, with the contribution of CYP450 vasodilator metabolites. This effect was the most prominent in the DM+HBO2 group of rats.The TBARS was significantly higher in both DM and DM+HBO2 groups compared to respective controls. eNOS expression was upregulated in the DM+HBO2 group compared to other groups, COX1 expression was upregulated in DM+HBO2 group compared to the control. CYP450-4A1/A2/A3protein expression was significantly higher expressed in both hyperbaric groups compared to their respective controls. In conclusion, HBO2 affected all three vasodilator pathways and shifted AChIR to CYP450 enzymes pathway.

hyperbaric oxygenation ; CYP450-isoformes ; NOS ; acetylcholine ; EETs ; diabetes mellitus

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