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Article

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

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Institute and Department of Physiology and Immunology, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia
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Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, 31000 Osijek, Croatia
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Department of Pathophysiology, Physiology and Immunology, Faculty of Dental Medicine and Health Studies, Josip Juraj Strossmayer University of Osijek, Crkvena ul. 21, 31000 Osijek, Croatia
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Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb, Trg Republike Hrvatske 14, 10000 Zagreb, Croatia
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Department of Drug Metabolism and Pharmacokinetics, Fidelta Ltd., Prilaz baruna Filipovića 29, 10000 Zagreb, Croatia
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Radiation Chemistry and Dosimetry Laboratory, Division of Materials Chemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia
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Department of Heart and Vascular Diseases, Osijek University Hospital, J. Huttlera 4, 31000 Osijek, Croatia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(17), 6353; https://doi.org/10.3390/ijms21176353
Received: 29 July 2020 / Revised: 26 August 2020 / Accepted: 29 August 2020 / Published: 1 September 2020
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. View Full-Text
Keywords: acetylcholine; aortic rings; epoxyeicosatrienoic acids; hyperbaric oxygenation; hypoxia; HIF-1α acetylcholine; aortic rings; epoxyeicosatrienoic acids; hyperbaric oxygenation; hypoxia; HIF-1α
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MDPI and ACS Style

Mihaljević, Z.; Matić, A.; Stupin, A.; Frkanec, R.; Tavčar, B.; Kelava, V.; Tartaro Bujak, I.; Kolobarić, N.; Kibel, A.; Drenjančević, I. Arachidonic Acid Metabolites of CYP450 Enzymes and HIF-1α Modulate Endothelium-Dependent Vasorelaxation in Sprague-Dawley Rats under Acute and Intermittent Hyperbaric Oxygenation. Int. J. Mol. Sci. 2020, 21, 6353. https://doi.org/10.3390/ijms21176353

AMA Style

Mihaljević Z, Matić A, Stupin A, Frkanec R, Tavčar B, Kelava V, Tartaro Bujak I, Kolobarić N, Kibel A, Drenjančević I. 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. 2020; 21(17):6353. https://doi.org/10.3390/ijms21176353

Chicago/Turabian Style

Mihaljević, Zrinka, Anita Matić, Ana Stupin, Ruža Frkanec, Branka Tavčar, Vanja Kelava, Ivana Tartaro Bujak, Nikolina Kolobarić, Aleksandar Kibel, and Ines Drenjančević. 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, no. 17: 6353. https://doi.org/10.3390/ijms21176353

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