Variability in flow-induced vasodilation mechanisms in cerebral arteries: the impact of different hyperbaric oxygen protocolsDrenjančević, Ines1,2,#; Jukić, Ivana1,2,#; Đambić, Vedran1; Stupin, Ana1,2; Kozina, Nataša1,2; Matić, Anita1,2,3; Šušnjara, Petar1,2,4; Kibel, Aleksandar1,2,5; Biljan, Darko6,7;Mihaljević, Zrinka 1Department of Physiology and Immunology, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia 2Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia 3Institute for Integrative Medicine, Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia 4Faculty of Kinesiology Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia 5International Medical Center Priora, Čepin, Croatia 6Department of Infectology and Dermatovenerology, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia 7Department of Dermatology and Venereology, Osijek University Hospital, Osijek, Croatia Abstract The present study aimed to assess the mechanisms of flow-induced dilation (FID) altered by acute/intermittent hyperbaric oxygenation (HBO2) in isolated middle cerebral arteries of healthy male Sprague‒Dawley rats (n = 96) and randomized to the Ac-HBO2 group (exposed to a single HBO2 session, 120 minutes of 100% O2 at 2.0 bars), the 4Dys-HBO2 group (4 consecutive days of single HBO2 sessions, analyzed on the fifth day), and the CTRL (untreated) group. Results demonstrated increased vascular oxidative stress and decreased vascular nitric oxide bioavailability, as measured by direct fluorescence microscopy, leading to attenuated FID in the Ac-HBO2 group compared with the CTRL and 4Dys-HBO2 groups. Superoxide scavenging restored FID. Moreover, the increased expression of antioxidative enzymes in the cerebral vasculature in the 4Dys-HBO2 group indicates the ability of intermittent HBO2 to activate antioxidative mechanisms. Importantly, the results suggest a switch or at least activation of the compensatory mechanism of FID after HBO2 from nitric oxide-dependent to epoxygenase metabolite-mediated via TRPV4 (transient receptor potential cation channel subfamily V member 4) and potassium channels, as demonstrated by increased protein expression of KCNMB1 (potassium calcium-activated channel subfamily M regulatory beta subunit 1), TRPV4, and Kir2 (a component of the inward rectifier-type potassium channel Kir2) in the vasculature. Overall, acute HBO2 modulates FID in cerebral vessels by increasing oxidative stress and altering the subsequent mechanisms of FID, which are mainly mediated by nitric oxide, while suppressing potassium and TRPV4 channel function/expression due to increased oxidative stress. Moreover, intermittent HBO2 activates antioxidative mechanisms and the compensatory mechanism of FID from nitric oxide-dependent to epoxygenase metabolite-mediated mechanisms via TRPV4, KCNMB1 and Kir2.1. 本研究旨在评估急性/间歇性高压氧（HBO₂）对健康雄性Sprague-Dawley大鼠（n=96）离体大脑中动脉血流介导舒张功能（FID）的调控机制。实验分为三组：Ac-HBO₂组（单次HBO₂暴露，2.0个大气压下100%氧气120分钟）、4Dys-HBO₂组（连续4天单次HBO₂暴露，第5天检测）和CTRL组（未处理）。 结果显示：
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