Variability in flow-induced vasodilation mechanisms in cerebral arteries: the impact of different hyperbaric oxygen protocols.

Abstract

The present study aimed to assess the mechanisms of flow-induced dilation (FID) altered by acute/intermittent hyperbaric oxygenation (HBO 2 ) in isolated middle cerebral arteries of healthy male Sprague‒Dawley rats ( n = 96) and randomized to the Ac-HBO 2 group (exposed to a single HBO 2 session, 120 minutes of 100% O 2 at 2.0 bars), the 4Dys-HBO 2 group (4 consecutive days of single HBO 2 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-HBO 2 group compared with the CTRL and 4Dys-HBO 2 groups. Superoxide scavenging restored FID. Moreover, the increased expression of antioxidative enzymes in the cerebral vasculature in the 4Dys-HBO 2 group indicates the ability of intermittent HBO 2 to activate antioxidative mechanisms. Importantly, the results suggest a switch or at least activation of the compensatory mechanism of FID after HBO 2 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 HBO 2 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 HBO 2 activates antioxidative mechanisms and the compensatory mechanism of FID from nitric oxide-dependent to epoxygenase metabolite-mediated mechanisms via TRPV4, KCNMB1 and Kir2.1.