Arachidonic Acid Metabolites of CYP450 Enzymes and HIF-1α Modulate Endothelium-Dependent Vasorelaxation in Sprague-Dawley Rats under Acute and Intermittent Hyperbaric Oxygenation.

Acetylcholine-induced vasorelaxation (AChIR) and responses to reduced pO₂ (hypoxia-induced relaxation (HIR), 0% O₂) were assessed in vitro in aortic rings of healthy male Sprague-Dawley rats (N = 252) under hyperbaric (HBO₂) protocols. The studied groups consisted of the CTRL group (untreated); the A-HBO₂ group (single HBO₂; 120 min of 100% O₂ at 2.0 bars); the 24H-HBO₂ group (examined 24 h after single exposure) and the 4D-HBO₂ group (four consecutive days of single HBO₂). AChIR, sensitivity to ACh and iNOS expression were decreased in the A-HBO₂ group. HIR was prostanoid- and epoxyeicosatrienoic acid (EET)-mediated. HIF-1α expression was increased in the 24H-HBO₂ and 4D-HBO₂ groups. LW6 (HIF-1α inhibitor) decreased HIR in the 24H-HBO₂ group. HBO₂ affected the expression of COX-1 and COX-2. CYP2c11 expression was elevated in the 24H-HBO₂ and 4D-HBO₂ groups. Concentrations of arachidonic acid (AA) metabolites 14(15)-DiHET, 11(12)-DiHET and 8(9)-DiHET were increased in A-HBO₂ and 24H-HBO_2. An increased concentration of 8(9)-EET was observed in the A-HBO₂ and 24h-HBO₂ groups vs. the CTRL and 4D-HBO₂ groups, and an increased concentration of 5(6)-DiHET was observed in the 24H-HBO₂ group vs. the 4D-HBO₂ group. The 20-HETE concentration was increased in the A-HBO₂ group. All were determined by LC-MS/MS of the aorta. The results show that AChIR in all groups is mostly NO-dependent. HIR is undoubtedly mediated by the CYP450 enzymes' metabolites of AA, whereas HIF-1α contributes to restored HIR. Vasoconstrictor metabolites of CYP450 enzymes contribute to attenuated AChIR and HIR in A-HBO₂. [ABSTRACT FROM AUTHOR]