Objective: To assess and elucidate the mechanisms of hyperbaric oxygenation (HBO2) effects on vascular reactivity to angiotensin-(1-7) [ANG-(1-7)] and angiotensin II (ANG II).
Methods: Rat aortic rings (HBO2 vs. control group) were used to test responses to ANG II, ANG II+ ANG-(1-7) or ANG-(1-7) after noradrenaline precontraction in the presence/absence of MS-PPOH, a specific CYP 450-epoxygenase inhibitor, and glibenclamide, a KATP channels inhibitor. mRNA expression studies of specific CYP isozymes have been conducted as well.
Results: The mean contraction (expressed as percent of maximal contraction) for ANG II was similar between groups. Contraction for ANG II + ANG-(1-7) was 15% +/- 10 (HBO2) and 20% +/- 9 (control). There was a significant decrease between the contraction response to ANG II (HBO2) and the response to ANG II + ANG-(1-7) in the HBO2 group, without such a difference within the control group. Mean percentage of noradrenaline precontraction decrease after ANG-(1-7) addition was significantly different [10% +/- 9 (control) and 19% +/- 11 (HBO2)]. The epoxygenase inhibitor MS-PPOH in HBO2 animals reversed these changes. Glibenclamide had no effect on relaxation in response to ANG-(1-7). Expression of CYP4A2, CYP4A3 and CYP2J3 mRNA was not significantly altered with HBO, whereas CYP4A1 was significantly upregulated.
Conclusions: Our results suggest a role for epoxyeicosatrienoic acids in modulating relaxation response to ANG-(1-7) with HBO2 that is conducted via potassium channels other than KATP channels. HBO2 increased the responses to ANG-(1-7) after precontraction with noradrenaline. The difference between the response to ANG II in the HBO2 group and ANG II + ANG-(1-7) in the HBO2 group (the contraction force of the peptide combination being lower), without such difference in the control group, suggests an influence ofHBO2 on vascular reactivity.