engleski

Hyperbaric oxygen treatment improves hypoxia-induced reactivity of isolated cerebral vessels of diabetic rats: role of ATP sensitive potassium channels

Aims: Our previous studies on animal models of diabetes mellitus (DM) demonstrated that the reactivity of resistance arteries to various stimuli is significantly impaired, which could be restored by hyperbaric oxygen treatment (HBOT). ATP sensitive potassium channels (KATP channels) play an important role in mediating several vasodilator responses. We aimed to evaluate the role of KATP channels and to evaluate the effects of HBOT on vasodilator responses to hypoxia (reduced pO2) of isolated middle cerebral arteries (MCA) of control and diabetic Sprague-Dawley male rats. Methods: Rats (12-weeks old ; duration of streptozocin-DM 6 weeks) were divided in 3 groups ; control (n=7), diabetic (n=6) and diabetic rats+HBOT (n=6). One group of rats was exposed to HBOT at 2, 0 atm, in duration of 120 minutes for 4 consecutive days. Isolated rat MCA were perfused and superfused with physiological salt solution equilibrated with control or reduced PO2 (~140 mmHg and ~35 mmHg, respectively) in absence or the presence of the KATP channel blocker glibenclamide. The diameter was measured by video-microscopy. Results are expressed as MEAN±SEM. One way ANOVA with appropriate post hoc test was performed for statistical analysis (Sigma Plot 11.0). Results: In the diabetic group, significantly reduced dilations of MCA in response to reduced pO2 compared to all other groups (11±1, N=6 (control) vs. 3±1, N=6 (DM), vs. 13±2, N=6 (DM+HBOT)) was found. The reduced dilator response to hypoxia was restored in DM+HBOT group. Also, glibenclamide completely eliminated vasodilator responses to hypoxia in MCA in all groups of rats. Conclusions: These results demonstrate that - regardless of the magnitude of responses - the hypoxia-induced dilator responses of MCA of healthy, diabetic and HBOT-treated diabetic rats are mediated via activation of KATP channels. Furthermore, HBOT restores the dilations of MCA of diabetic rats in response to reduced pO2, suggesting that HBOT improves cerebrovascular function and tissue perfusion in DM. Support: grant of Croatian Ministry of Science, Education and Sports, #219-2160133-2034.

hypoxia; potassium channels; hyperbaric oxygen

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