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

Mihaljević, Zrinka; Matić, Anita; Stupin, Ana; Frkanec, Ruža; Kelava, Vanja; Tartaro Bujak, Ivana; Kolobarić, Nikolina; Kibel, Aleksandar; Drenjančević, Ines (2020) Arachidonic Acid Metabolites of CYP450 Enzymes and HIF-1α Modulate Endothelium-Dependent Vasorelaxation in Sprague-Dawley Rats under Acute and Intermittent Hyperbaric Oxygenation. International journal of molecular sciences, 21 (17). ISSN 1422-0067

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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.

Item Type:	Article
Uncontrolled Keywords:	acetylcholine ; aortic rings ; epoxyeicosatrienoic acids ; hyperbaric oxygenation ; hypoxia ; HIF-1α
Subjects:	BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences
Divisions:	Division of Materials Physics
Projects:	Project title Project leader Project code Project type Djelovanje kisika na vaskularnu funkciju u zdravlju i bolesti- Ines Drenjančević 219-2160133-2034 MZOS
Depositing User:	Ivana Tartaro Bujak
Date Deposited:	16 Nov 2020 12:54
URI:	http://fulir.irb.hr/id/eprint/6010
DOI:	doi.org/10.3390/ijms21176353

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