ArticleThe Journal of biological chemistry2016
20-Hydroxyeicosatetraenoic Acid (HETE)-dependent Hypertension in Human Cytochrome P450 (CYP) 4A11 Transgenic Mice: NORMALIZATION OF BLOOD PRESSURE BY SODIUM RESTRICTION, HYDROCHLOROTHIAZIDE, OR BLOCKADE OF THE TYPE 1 ANGIOTENSIN II RECEPTOR.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- Article
- Liver CYP4A autophagic lysosomal degradation: A major role for the autophagic receptor SQSTM1/p62 through an uncommon target interaction site.Molecular pharmacology · 2025Article
- The fatty acid omega hydroxylase genes (CYP4 family) in the progression of metabolic dysfunction-associated steatotic liver disease (MASLD): An RNA sequence database analysis and review.Biochemical pharmacology · 2024Review
- 20-Hydroxyeicosatetraenoic acid (20-HETE): Bioactions, receptors, vascular function, cardiometabolic disease and beyond.Advances in pharmacology (San Diego, Calif.) · 2023Article
- Eicosanoids and other oxylipins in liver injury, inflammation and liver cancer development.Frontiers in physiology · 2023Review
- The CYP/20-HETE/GPR75 axis in hypertension.Advances in pharmacology (San Diego, Calif.) · 2022Review
- Treatment of Primary Aldosteronism Increases Plasma Epoxyeicosatrienoic Acids.Hypertension (Dallas, Tex. : 1979) · 2021Article
- Oxylipin Response to Acute and Chronic Exercise: A Systematic Review.Metabolites · 2020Review
- Proximal tubular-targeted overexpression of the Cyp4a12-20-HETE synthase promotes salt-sensitive hypertension in male mice.American journal of physiology. Regulatory, integrative and comparative physiology · 2020Article
- Genetic polymorphisms associated with reactive oxygen species and blood pressure regulation.The pharmacogenomics journal · 2019Review
- Cytochrome P450 research andThe Journal of biological chemistry · 2019Review
- P450-Humanized and Human Liver Chimeric Mouse Models for Studying Xenobiotic Metabolism and Toxicity.Drug metabolism and disposition: the biological fate of chemicals · 2018Review
- 20-Hydroxyeicosatetraenoic acid antagonist attenuates the development of malignant hypertension and reverses it once established: a study in Cyp1a1-Ren-2 transgenic rats.Bioscience reports · 2018Article
- Conflicting roles of 20-HETE in hypertension and renal end organ damage.European journal of pharmacology · 2018Review
- 20-HETE: Hypertension and Beyond.Hypertension (Dallas, Tex. : 1979) · 2018Review
- Sulfenylation of Human Liver and Kidney Microsomal Cytochromes P450 and Other Drug-Metabolizing Enzymes as a Response to Redox Alteration.Molecular & cellular proteomics : MCP · 2018Article
- Transcriptomic profile analysis of brain microvascular pericytes in spontaneously hypertensive rats by RNA-Seq.American journal of translational research · 2018Article
- Expression and Functional Characterization of Breast Cancer-Associated Cytochrome P450 4Z1 inDrug metabolism and disposition: the biological fate of chemicals · 2017Article
- The Blood Pressure-Lowering Effect of 20-HETE Blockade inThe Journal of pharmacology and experimental therapeutics · 2017Article
- Effect of Cytochrome P450 Metabolites of Arachidonic Acid in Nephrology.Journal of the American Society of Nephrology : JASN · 2017Review
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7 authors at 3 institutions in 1 country.
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Abstract
Male and female homozygous 129/Sv mice carrying four copies of the human cytochrome P450 4A11 gene (CYP4A11) under control of its native promoter (B-129/Sv-4A11(+/+)) develop hypertension (142 ± 8 versus 113 ± 7 mm Hg systolic blood pressure (BP)), and exhibit increased 20-hydroxyeicosatetraenoic acid (20-HETE) in kidney and urine. The hypertension is reversible by a low-sodium diet and by the CYP4A inhibitor HET0016. B-129/Sv-4A11(+/+) mice display an 18% increase of plasma potassium (p < 0.02), but plasma aldosterone, angiotensin II (ANGII), and renin activities are unchanged. This phenotype resembles human genetic disorders with elevated activity of the sodium chloride co-transporter (NCC) and, accordingly, NCC abundance is increased by 50% in transgenic mice, and NCC levels are normalized by HET0016. ANGII is known to increase NCC abundance, and renal mRNA levels of its precursor angiotensinogen are increased 2-fold in B-129/Sv-4A11(+/+), and blockade of the ANGII receptor type 1 with losartan normalizes BP. A pro-hypertensive role for 20-HETE was implicated by normalization of BP and reversal of renal angiotensin mRNA increases by administration of the 20-HETE antagonists 2-((6Z,15Z)-20-hydroxyicosa-6,15-dienamido)acetate or (S)-2-((6Z,15Z)-20-hydroxyicosa-6,15-dienamido)succinate. SGK1 expression is also increased in B-129/Sv-4A11(+/+) mice and paralleled increases seen for NCC. Losartan, HET0016, and 20-HETE antagonists each normalized SGK1 mRNA expression. These results point to a potential 20-HETE dependence of intrarenal angiotensinogen production and ANGII receptor type 1 activation that are associated with increases in NCC and SGK1 and identify elevated P450 4A11 activity and 20-HETE as potential risk factors for salt-sensitive human hypertension by perturbation of the renal renin-angiotensin axis.
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