hrvatski

Ion channels modulation after acute and intermittent hyperbaric oxygen exposure – changes in vascular relaxation mechanism

INTRODUCTION: Hyperbaric oxygenation (HBO2) effects on vascular reactivity in aortic rings vary, depending on the applied protocols. Acute changes in pO2 affect K+ channels, and HBO2 seems to modulate transient potential receptor channel (TRP) on the endothelial cell membrane. AIM: This study assessed the effect of different HBO2 protocols on the mechanisms of flow induced dilation (FID) and the role of K+ and TRP channels in middle cerebral arteries (MCA) of Sprague-Dawley rats. MATERIALS AND METHODS: 11 week old male rats (N=6 per group) were divided in: CTRL (control group of rats) ; A-HBO2 (acute exposure to 100% oxygen ; 2bar/2hrs) and 4D-HBO2 (rats exposed to HBO2 for four consecutive days and examined on the 5th day). Rats were anesthetized with ketamine-chloride (75 mg/kg) and midazolam (0.5 mg/kg), decapitated and blood vessels were collected. FID was assessed in isolated cannulated and pressurized MCA, (Myograph Pressure System Model 110P MyoView Version 1.2.0 DMT ; Danish Myo Technology). FID was evaluated over pressure gradient at Δ10 mmHg, Δ20 mmHg, Δ40 mmHg, Δ60 mmHg and Δ100 mmHg, with/without agonist and antagonists for large conductance Ca2+-activated K+- channel (KCa2+, NS-1619 and iberiotoxin) ; ATP- sensitive potassium channels (KATP, cromakalim and glibenclamide) and TRPV4 (GSK1016790A and RN-1734). Protein levels of TRPV4 and KCNMB1 were assessed by Western blot method. All experimental procedures conformed to the European Guidelines for the Care and Use of Laboratory Animals (directive 86/609) and were approved by the local and national Ethical Committee. RESULTS: FID in A-HBO2 group was significantly impaired compared to CTRL and 4DHBO2 groups. Agonists of ion channels restored FID in A-HBO2 groups and antagonists (iberiotoxin, glibenclamide and RN-1734) inhibit FID without additional effect in 4DHBO2 group compared to CTRL. Protein levels of KCNMB1 and TRPV4 were increased in 4DHBO2 group compared to CTRL. CONCLUSION: Results suggest ion channels’ modulation depending on the HBO2 protocol. FUNDING: This study was supported by institutional grants from the Faculty of Medicine Osijek VIF-2016- MEFOS grant (PI Ines Drenjančević) and VIF-2018- MEFOS grant (PI Anita Matic) and IP2-2019-MEFOS (PI Zrinka Mihaljević).

hyperbaric oxygen ; flow induced dilation ; cerebral circulation ; endothelium ; membrane ion channels

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