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

Abstract

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-HBO2. 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.

Exhaled breath condensate profiles of U.S. Navy divers following prolonged hyperbaric oxygen (HBO) and nitrogen-oxygen (Nitrox) chamber exposures

“…PGJ2 is neurotoxic and induces apoptosis, oxidative stress, and the accumulation of ubiquitinated proteins in the brain. 11(12)-DiHET is a cytochrome P450-monooxygenase system metabolite of arachidonic acid that has been shown to increase immediately and 24 h after hyperbaric hyperoxia in rats [26], though it decreased following our hyperoxic exposure study. 11(12)-DiHET produces vasorelaxation in isolated porcine coronary artery rings precontracted with a thromboxane mimetic [27].…”

Vascular Effects of Polyphenols from Agrimonia eupatoria L. and Role of Isoquercitrin in Its Vasorelaxant Potential in Human Arteries

“…However, experiments with the IP receptor antagonist Ro 1138452 did not confirm our hypothesis ( Figure 2 E). Beyond prostacyclin, other vasodilator metabolites have been described, such as epoxyeicosatrienoic acids or EETs (namely 14,15-EET and 11,12-EET), cytochrome P450 metabolites and prostaglandin D2 and E2 also via COX [ 13 ]. Previous evidence suggests that 11,12-EET elicits relaxation in ITA through the activation of BK Ca channels and the vanilloid transient receptor potential channel 4 and canonical transient receptor potential channel 1 in smooth muscle cells [ 14 , 15 ].…”

Consumption of Nutritionally Enriched Hen Eggs Enhances Endothelium-Dependent Vasodilation via Cyclooxygenase Metabolites in Healthy Young People—A Randomized Study

“…To determine the relative protein expression of iNOS, eNOS, nNOS, COX-1 and COX-2 from isolated PBMC, Western blot was carried out according to the well-established method at our laboratory [ 30 , 31 , 32 ]. Homogenization buffer (50 mM HEPES 150 mM NaCl, 1 mM EDTA, 10% glycerol, 1% TRIXON-X), protease inhibitor cocktail 0.4 µL/100 µL (Complete mini EDTA free Protease inhibitor cocktail, Roche Diagnostics GmbH, Mannheim, Germany) was used to homogenize PBMC.…”