{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T23:05:02Z","timestamp":1768259102893,"version":"3.49.0"},"reference-count":63,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006588","name":"Ministarstvo Znanosti, Obrazovanja i Sporta","doi-asserted-by":"publisher","award":["219-2160133-2034"],"award-info":[{"award-number":["219-2160133-2034"]}],"id":[{"id":"10.13039\/501100006588","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medicinski fakultet Osijek","award":["VIF Drenjan\u010devi\u0107-2016-MEFOS"],"award-info":[{"award-number":["VIF Drenjan\u010devi\u0107-2016-MEFOS"]}]},{"name":"Medicinski fakultet Osijek","award":["VIF Mati\u0107-2018-MEFOS"],"award-info":[{"award-number":["VIF Mati\u0107-2018-MEFOS"]}]},{"name":"Medicinski fakultet Osijek","award":["IP2-2019-MEFOS"],"award-info":[{"award-number":["IP2-2019-MEFOS"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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-1\u03b1 expression was increased in the 24H-HBO2 and 4D-HBO2 groups. LW6 (HIF-1\u03b1 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\u2019 metabolites of AA, whereas HIF-1\u03b1 contributes to restored HIR. Vasoconstrictor metabolites of CYP450 enzymes contribute to attenuated AChIR and HIR in A-HBO2.<\/jats:p>","DOI":"10.3390\/ijms21176353","type":"journal-article","created":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T14:21:10Z","timestamp":1598970070000},"page":"6353","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Arachidonic Acid Metabolites of CYP450 Enzymes and HIF-1\u03b1 Modulate Endothelium-Dependent Vasorelaxation in Sprague-Dawley Rats under Acute and Intermittent Hyperbaric Oxygenation"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6631-071X","authenticated-orcid":false,"given":"Zrinka","family":"Mihaljevi\u0107","sequence":"first","affiliation":[{"name":"Institute and Department of Physiology and Immunology, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia"},{"name":"Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, 31000 Osijek, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita","family":"Mati\u0107","sequence":"additional","affiliation":[{"name":"Institute and Department of Physiology and Immunology, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia"},{"name":"Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, 31000 Osijek, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7446-0021","authenticated-orcid":false,"given":"Ana","family":"Stupin","sequence":"additional","affiliation":[{"name":"Institute and Department of Physiology and Immunology, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia"},{"name":"Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, 31000 Osijek, Croatia"},{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ru\u017ea","family":"Frkanec","sequence":"additional","affiliation":[{"name":"Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb, Trg Republike Hrvatske 14, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Branka","family":"Tav\u010dar","sequence":"additional","affiliation":[{"name":"Department of Drug Metabolism and Pharmacokinetics, Fidelta Ltd., Prilaz baruna Filipovi\u0107a 29, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanja","family":"Kelava","sequence":"additional","affiliation":[{"name":"Department of Drug Metabolism and Pharmacokinetics, Fidelta Ltd., Prilaz baruna Filipovi\u0107a 29, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1396-164X","authenticated-orcid":false,"given":"Ivana","family":"Tartaro Bujak","sequence":"additional","affiliation":[{"name":"Radiation Chemistry and Dosimetry Laboratory, Division of Materials Chemistry, Ru\u0111er Bo\u0161kovi\u0107 Institute, Bijeni\u010dka cesta 54, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5649-8317","authenticated-orcid":false,"given":"Nikolina","family":"Kolobari\u0107","sequence":"additional","affiliation":[{"name":"Institute and Department of Physiology and Immunology, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia"},{"name":"Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, 31000 Osijek, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandar","family":"Kibel","sequence":"additional","affiliation":[{"name":"Institute and Department of Physiology and Immunology, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia"},{"name":"Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, 31000 Osijek, Croatia"},{"name":"Department of Heart and Vascular Diseases, Osijek University Hospital, J. Huttlera 4, 31000 Osijek, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4964-7721","authenticated-orcid":false,"given":"Ines","family":"Drenjan\u010devi\u0107","sequence":"additional","affiliation":[{"name":"Institute and Department of Physiology and Immunology, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, J. 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Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"H981","DOI":"10.1152\/ajpheart.2001.281.3.H981","article-title":"Vascular endothelial dysfunction: Does tetrahydrobiopterin play a role?","volume":"281","author":"Katusic","year":"2001","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1161\/01.RES.88.2.e14","article-title":"Mechanisms underlying endothelial dysfunction in diabetes mellitus","volume":"88","author":"Hink","year":"2001","journal-title":"Circ. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1159\/000068938","article-title":"Lack of Nitric Oxide Mediation of Flow-Dependent Arteriolar Dilation in Type I Diabetes Is Restored by Sepiapterin","volume":"40","author":"Bagi","year":"2003","journal-title":"J. Vasc. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"H188","DOI":"10.1152\/ajpheart.00504.2004","article-title":"Restoration of normal vascular relaxation mechanisms in cerebral arteries by chromosomal substitution in consomic SS.13BN rats","volume":"289","author":"Phillips","year":"2005","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_7","first-page":"787","article-title":"Hyperbaric oxygenation affects the mechanisms of acetylcholine-induced relaxation in diabetic rats","volume":"43","author":"Unfirer","year":"2017","journal-title":"Undersea Hyperb. Med."},{"key":"ref_8","first-page":"1053","article-title":"Effects of hyperbaric oxygenation on vascular reactivity to angiotensin II and angiotensin-(1-7) in rats","volume":"39","author":"Kibel","year":"2012","journal-title":"Undersea Hyperb. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1177\/1479164114553424","article-title":"Hyperbaric oxygenation modulates vascular reactivity to angiotensin-(1-7) in diabetic rats: Potential role of epoxyeicosatrienoic acids","volume":"12","author":"Kibel","year":"2014","journal-title":"Diabetes Vasc. Dis. Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Lenasi, H. (2016). The Metabolites of Arachidonic Acid in Microvascular Function \/\/ Microcirculation Revisited\u2013From Molecules to Clinical Practice, IntechOpen.","DOI":"10.5772\/61893"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1161\/01.RES.83.9.932","article-title":"Epoxyeicosatrienoic acids and dihydroxyeicosatrienoic acids are potent vasodilators in the canine coronary microcirculation","volume":"83","author":"Oltman","year":"1998","journal-title":"Circ. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1097\/FJC.0b013e318273b007","article-title":"Epoxyeicosatrienoic Acid Pathway in Human Health and Diseases","volume":"61","author":"Bellien","year":"2013","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.prostaglandins.2014.05.001","article-title":"Vasodilatory effect of 14,15-epoxyeicosatrienoic acid on mesenteric arteries in hypertensive and aged rats","volume":"112","author":"Yang","year":"2014","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/aap.12052","article-title":"11,12-Epoxyeicosatrienoic acid induces vasodilator response in the rat perfused mesenteric vasculature","volume":"37","author":"Bihzad","year":"2017","journal-title":"Auton. Autacoid Pharmacol."},{"key":"ref_15","unstructured":"Drenjan\u010devi\u0107, I. (2018). Mechanisms of HBO-Induced Vascular Functional Changes in Diabetic Animal Models. Hyperbaric Oxygen Treatment in Research and Clinical Practice, IntechOpen."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1097\/MNH.0b013e32835d911e","article-title":"Role of cytochrome P450 epoxygenase in regulating renal membrane transport and hypertension","volume":"22","author":"Capdevila","year":"2013","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1161\/01.RES.79.1.54","article-title":"Identification of a Putative Microvascular Oxygen Sensor","volume":"79","author":"Harder","year":"1996","journal-title":"Circ. Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Mihaljevi\u0107, Z., Matic, A., Stupin, A., Rasic, L., Jukic, I., and Drenjancevic-Peric, I. (2018). Acute Hyperbaric Oxygenation, Contrary to Intermittent Hyperbaric Oxygenation, Adversely Affects Vasorelaxation in Healthy Sprague-Dawley Rats due to Increased Oxidative Stress. Oxidative Med. Cell. Longev., 1\u201315.","DOI":"10.1155\/2018\/7406027"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5680","DOI":"10.1073\/pnas.88.13.5680","article-title":"Hypoxia-inducible nuclear factors bind to an enhancer element located 3\u2019 to the human erythropoietin gene","volume":"88","author":"Semenza","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"32253","DOI":"10.1074\/jbc.271.50.32253","article-title":"Activation of hypoxia-inducible transcription factor depends primarly upon redox-sensitive stabilization of its \u03b1 subunit","volume":"271","author":"Huang","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/wrr.12253","article-title":"Hyperbaric oxygen therapy activates hypoxia-inducible factor 1 (HIF-1), which contributes to improved wound healing in diabetic mice","volume":"23","author":"Sunkari","year":"2015","journal-title":"Wound Repair Regen."},{"key":"ref_22","first-page":"609","article-title":"Oxygen(es) and the hypoxia \u2013 inducible factor-1","volume":"378","author":"Wenger","year":"1997","journal-title":"Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1093\/carcin\/19.11.1913","article-title":"Adaptive protection against the induction of oxidative DNA damage after hyperbaric oxygen treatment","volume":"19","author":"Rothfuss","year":"1998","journal-title":"Carcinogenesis"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0027-5107(02)00213-0","article-title":"Investigations on the mechanism of hyperbaric oxygen (HBO)-induced adaptive protection against oxidative stress","volume":"508","author":"Rothfuss","year":"2002","journal-title":"Mutat. Res. Mol. Mech. Mutagen."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1016\/j.lfs.2006.11.043","article-title":"Preconditioning with hyperbaric oxygen induces tolerance against oxidative injury via increased expression of heme oxygenase-1 in primary cultured spinal cord neurons","volume":"80","author":"Li","year":"2007","journal-title":"Life Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3139","DOI":"10.1161\/STROKEAHA.109.549774","article-title":"Cyclo-oxygenase-2 mediates hyperbaric oxygen preconditioning-induced neuroprotection in the mouse model of surgical brain injury","volume":"40","author":"Jadhav","year":"2009","journal-title":"Stroke"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"H1982","DOI":"10.1152\/ajpheart.01261.2007","article-title":"Role of EDHF in type 2 diabetes-induced endothelial dysfunction","volume":"295","author":"Park","year":"2008","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_28","unstructured":"Gesell, L.B. (2008). Hyperbaric Oxygen Therapy Indications, Undersea and Hyperbaric Medical Society. [12th ed.]."},{"key":"ref_29","first-page":"319","article-title":"Blood pressure, acid-base and blood gas status and indicators of oxidative stress in healthy male rats exposed to acute hyperbaric oxygenation","volume":"40","author":"Kibel","year":"2013","journal-title":"Undersea Hyperb. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"H580","DOI":"10.1152\/ajpheart.1994.267.2.H580","article-title":"Role of endothelium and arterial K+ channels in mediating hypoxic dilation of middle cerebral arteries","volume":"267","author":"Fredricks","year":"1994","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1159\/000051061","article-title":"Relative contributions of cyclooxygenase and cytochrome P450 \u03c9-hydroxylase-dependent pathways to hypoxic dilation of skeletal muscle resistance arteries","volume":"38","author":"Frisbee","year":"2001","journal-title":"J. Vasc. Res."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Feletou, M., and Vanhoutte, P. (2005). EDHF and the Physiological Control of Blood Flow in EDHF: The Complete Story, CRC Taylor and Francis.","DOI":"10.1201\/9780367800970"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1242\/jcs.00318","article-title":"Intracellular localisation of human HIF-1alpha hydroxylases: Implications for oxygen sensing","volume":"116","author":"Metzen","year":"2003","journal-title":"J. Cell Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1046\/j.1365-2613.1998.00088.x","article-title":"Hypoxia-mediated regulation of gene expression in mammalian cells","volume":"79","author":"Shih","year":"1998","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"22642","DOI":"10.1074\/jbc.272.36.22642","article-title":"Hypoxia-inducible factor 1alpha (HIF-1alpha) protein is rapidly degraded by the ubiquitin-proteasome system under normoxic conditions. Its stabilization by hypoxia depends on redox-induced changes","volume":"272","author":"Salceda","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0955-0674(00)00194-0","article-title":"HIF-1 and mechanisms of hypoxia sensing","volume":"13","author":"Semenza","year":"2001","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"L922","DOI":"10.1152\/ajplung.00014.2002","article-title":"Hypoxic but not anoxic stabilization of HIF-1\u03b1 requires mitochondrial reactive oxygen species","volume":"283","author":"Schroedl","year":"2002","journal-title":"Am. J. Physiol. Cell. Mol. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1182\/blood-2004-07-2958","article-title":"Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1","volume":"105","author":"Manalo","year":"2005","journal-title":"Blood"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1254\/jphs.08122FP","article-title":"Epoxyeicosatrienoic acids and\/or their metabolites promote hypoxic response of cells","volume":"108","author":"Suzuki","year":"2008","journal-title":"J. Pharmacol. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1097\/SHK.0b013e31816a2136","article-title":"Regulatory effects of hypoxia-inducible factor 1 alpha on vascular reactivity and its mechanisms following hemorragic shock in rats","volume":"30","author":"Zhang","year":"2008","journal-title":"Shock"},{"key":"ref_41","first-page":"H1546","article-title":"Role of cytochrome P-450 4A in oxygen sensing and NO production in rat cremaster resistance arteries","volume":"277","author":"Kerkhof","year":"1999","journal-title":"Am. J. Physiol. Content"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1152\/japplphysiol.00323.2007","article-title":"Mechanism of ischemic tolerance induced by hyperbaric oxygen preconditioning involves upregulation of hypoxia-inducible factor - 1\u03b1 and erithropoietin in rats","volume":"104","author":"Gu","year":"2008","journal-title":"J. Appl. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.brainres.2008.03.027","article-title":"Up-regulated HIF-1\u03b1 is involved in the hypoxic tolerance induced by hyperbaric oxygen preconditioning","volume":"1212","author":"Peng","year":"2008","journal-title":"Brain Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1097\/MPA.0b013e31819cac24","article-title":"Down-Regulation of Hypoxia-Inducible Factor-1\u03b1 by Hyperbaric Oxygen Attenuates the Severity of Acute Pancreatitis in Rats","volume":"38","author":"Bai","year":"2009","journal-title":"Pancreas"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3897","DOI":"10.3760\/cma.j.issn.0366-6999.20130571","article-title":"Hyperbaric oxygen intervention on expression of hypoxia-inducible factor-1\u03b1 and vascular endothelial growth factor in spinal cord injury models in rats","volume":"126","author":"Zhou","year":"2013","journal-title":"Chin. Med. J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6683","DOI":"10.1158\/0008-5472.CAN-06-0425","article-title":"Direct Transcriptional Up-regulation of Cyclooxygenase-2 by Hypoxia-Inducible Factor (HIF)-1 Promotes Colorectal Tumor Cell Survival and Enhances HIF-1 Transcriptional Activity during Hypoxia","volume":"66","author":"Kaidi","year":"2006","journal-title":"Cancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"567","DOI":"10.2174\/138920009789375397","article-title":"The transcriptional regulation of the human CYP2C genes","volume":"10","author":"Chen","year":"2009","journal-title":"Curr. Drug Metab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1161\/01.RES.67.5.1082","article-title":"5,6-epoxyeicosatrienoic acid, a novel arachidonate metabolite. Mechanism of vasoactivity in the rat","volume":"67","author":"Carroll","year":"1990","journal-title":"Circ. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"F781","DOI":"10.1152\/ajprenal.1990.258.4.F781","article-title":"Cytochrome P-450 arachidonate metabolites in rat kidney: Characterization and hemodynamic responses","volume":"258","author":"Takahashi","year":"1990","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2364","DOI":"10.1681\/ASN.V7112364","article-title":"Actions of epoxygenase metabolites on the preglomerular vasculature","volume":"7","author":"Imig","year":"1996","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1152\/physrev.00021.2001","article-title":"P-450 Metabolites of Arachidonic Acid in the Control of Cardiovascular Function","volume":"82","author":"Roman","year":"2002","journal-title":"Physiol. Rev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1113\/EP086402","article-title":"Hyperbaric oxygenation and 20-hydroxyeicosatetreanoic acid inhibition reduce stroke volume in female diabetic Sprague-Dawley rats","volume":"102","author":"Novak","year":"2017","journal-title":"Exp. Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1080\/02699052.2016.1195518","article-title":"Is shorter transient middle cerebral artery occlusion (t-MCAO) duration better in stroke experiments on diabetic female Sprague Dawely rats?","volume":"30","author":"Mihalj","year":"2016","journal-title":"Brain Inj."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4917","DOI":"10.1113\/JP272297","article-title":"Attenuated flow-induced dilatation of middle cerebral arteries is related to increased vascular oxidative stress in rats on a short-term high salt diet","volume":"594","author":"Cosic","year":"2016","journal-title":"J. Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"H718","DOI":"10.1152\/ajpheart.00097.2018","article-title":"High salt intake shifts the mechanisms of flow-induced dilation in the middle cerebral arteries of Sprague-Dawley rats","volume":"315","author":"Stupin","year":"2018","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/0003-2697(87)90021-2","article-title":"Single-step method of RNA isolation by acid guanidinium thiocyanate\u2013phenol\u2014Chloroform extraction","volume":"162","author":"Chomczynski","year":"1987","journal-title":"Anal. Biochem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2\u2212\u0394\u0394CT Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1016\/j.jpba.2006.10.009","article-title":"A liquid chromatography\/mass spectrometric method for simultaneous analysis of arachidonic acid and its endogenous eicosanoid metabolites prostaglandins, dihydroxyeicosatrienoic acids, hydroxyeicosatetraenoic acids, and epoxyeicosatrienoic acids in rat brain tissue","volume":"43","author":"Yue","year":"2007","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2915","DOI":"10.1096\/fj.13-241927","article-title":"Vascular characterization of mice with endothelial expression of cytochrome P450 4F2","volume":"28","author":"Cheng","year":"2014","journal-title":"FASEB J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.jchromb.2014.03.007","article-title":"A review of analytical methods for eicosanoids in brain tissue","volume":"964","author":"Puppolo","year":"2014","journal-title":"J. Chromatogr. B"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1248\/bpb.b15-00480","article-title":"Simultaneous Determination Method of Epoxyeicosatrienoic Acids and Dihydroxyeicosatrienoic Acids by LC-MS\/MS System","volume":"38","author":"Mukai","year":"2015","journal-title":"Biol. Pharm. Bull."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Wang, W., Qin, S., Li, L., Chen, X., Wang, Q., and Wei, J. (2015). An Optimized High Throughput Clean-Up Method Using Mixed-Mode SPE Plate for the Analysis of Free Arachidonic Acid in Plasma by LC-MS\/MS. Int. J. Anal. Chem., 1\u20136.","DOI":"10.1155\/2015\/374819"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.jchromb.2013.08.001","article-title":"Development of a high-throughput ultra performance liquid chromatography\u2013mass spectrometry assay to profile 18 eicosanoids as exploratory biomarkers for atherosclerotic diseases","volume":"936","author":"Rago","year":"2013","journal-title":"J. Chromatogr. 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