Evidence map›Paper›PMID 26928804›Full record

ArticleHypertension (Dallas, Tex. : 1979)2016

6β-Hydroxytestosterone, a Cytochrome P450 1B1-Testosterone-Metabolite, Mediates Angiotensin II-Induced Renal Dysfunction in Male Mice.

Ajeeth K Pingili, Shyamala Thirunavukkarasu, Mehmet Kara, David D Brand, Akemi Katsurada, Dewan S A Majid, L Gabriel Navar, Frank J Gonzalez, Kafait U Malik

Open access · bronzeAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Hypertension (Dallas, Tex. : 1979), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.2field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Article
  3. CYP1B1 as a therapeutic target in cardio-oncology.Clinical science (London, England : 1979) · 2020
    Article
  4. Article
  5. Article
  6. Article
  7. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Ajeeth K PingiliFrom the Department of Pharmacology (A.K.P., S.T., M.K., K.U.M.) and Department of Medicine and Microbiology, Immunology and Biochemistry (D.D.B.), College of Medicine, University of Tennessee Health Science Center, Memphis; Veterans Affairs Medical Center, Memphis, TN (D.D.B.); Tulane Hypertension and Renal Center of Excellence, Department of Physiology, School of Medicine, Tulane University, New Orleans, LA (A.K., D.S.A.M., L.G.N.); and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD (F.J.G.).
Shyamala ThirunavukkarasuFrom the Department of Pharmacology (A.K.P., S.T., M.K., K.U.M.) and Department of Medicine and Microbiology, Immunology and Biochemistry (D.D.B.), College of Medicine, University of Tennessee Health Science Center, Memphis; Veterans Affairs Medical Center, Memphis, TN (D.D.B.); Tulane Hypertension and Renal Center of Excellence, Department of Physiology, School of Medicine, Tulane University, New Orleans, LA (A.K., D.S.A.M., L.G.N.); and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD (F.J.G.).
Mehmet KaraFrom the Department of Pharmacology (A.K.P., S.T., M.K., K.U.M.) and Department of Medicine and Microbiology, Immunology and Biochemistry (D.D.B.), College of Medicine, University of Tennessee Health Science Center, Memphis; Veterans Affairs Medical Center, Memphis, TN (D.D.B.); Tulane Hypertension and Renal Center of Excellence, Department of Physiology, School of Medicine, Tulane University, New Orleans, LA (A.K., D.S.A.M., L.G.N.); and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD (F.J.G.).
David D BrandFrom the Department of Pharmacology (A.K.P., S.T., M.K., K.U.M.) and Department of Medicine and Microbiology, Immunology and Biochemistry (D.D.B.), College of Medicine, University of Tennessee Health Science Center, Memphis; Veterans Affairs Medical Center, Memphis, TN (D.D.B.); Tulane Hypertension and Renal Center of Excellence, Department of Physiology, School of Medicine, Tulane University, New Orleans, LA (A.K., D.S.A.M., L.G.N.); and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD (F.J.G.).
Akemi KatsuradaFrom the Department of Pharmacology (A.K.P., S.T., M.K., K.U.M.) and Department of Medicine and Microbiology, Immunology and Biochemistry (D.D.B.), College of Medicine, University of Tennessee Health Science Center, Memphis; Veterans Affairs Medical Center, Memphis, TN (D.D.B.); Tulane Hypertension and Renal Center of Excellence, Department of Physiology, School of Medicine, Tulane University, New Orleans, LA (A.K., D.S.A.M., L.G.N.); and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD (F.J.G.).
Dewan S A MajidFrom the Department of Pharmacology (A.K.P., S.T., M.K., K.U.M.) and Department of Medicine and Microbiology, Immunology and Biochemistry (D.D.B.), College of Medicine, University of Tennessee Health Science Center, Memphis; Veterans Affairs Medical Center, Memphis, TN (D.D.B.); Tulane Hypertension and Renal Center of Excellence, Department of Physiology, School of Medicine, Tulane University, New Orleans, LA (A.K., D.S.A.M., L.G.N.); and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD (F.J.G.).
L Gabriel NavarFrom the Department of Pharmacology (A.K.P., S.T., M.K., K.U.M.) and Department of Medicine and Microbiology, Immunology and Biochemistry (D.D.B.), College of Medicine, University of Tennessee Health Science Center, Memphis; Veterans Affairs Medical Center, Memphis, TN (D.D.B.); Tulane Hypertension and Renal Center of Excellence, Department of Physiology, School of Medicine, Tulane University, New Orleans, LA (A.K., D.S.A.M., L.G.N.); and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD (F.J.G.).
Frank J GonzalezFrom the Department of Pharmacology (A.K.P., S.T., M.K., K.U.M.) and Department of Medicine and Microbiology, Immunology and Biochemistry (D.D.B.), College of Medicine, University of Tennessee Health Science Center, Memphis; Veterans Affairs Medical Center, Memphis, TN (D.D.B.); Tulane Hypertension and Renal Center of Excellence, Department of Physiology, School of Medicine, Tulane University, New Orleans, LA (A.K., D.S.A.M., L.G.N.); and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD (F.J.G.).
Kafait U MalikFrom the Department of Pharmacology (A.K.P., S.T., M.K., K.U.M.) and Department of Medicine and Microbiology, Immunology and Biochemistry (D.D.B.), College of Medicine, University of Tennessee Health Science Center, Memphis; Veterans Affairs Medical Center, Memphis, TN (D.D.B.); Tulane Hypertension and Renal Center of Excellence, Department of Physiology, School of Medicine, Tulane University, New Orleans, LA (A.K., D.S.A.M., L.G.N.); and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD (F.J.G.). kmalik@uthsc.edu.
Tulane University · USVeterans Health Administration · US

Funding

Angiotensins, Prostaglandins and Adrenergic InteractionsR01HL019134 · NHLBI · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI KAFAIT U MALIK · 1985 to 2026
$14.7M
Translational Research in Hypertension and Renal BiologyP30GM103337 · NIGMS · TULANE UNIVERSITY OF LOUISIANA · PI HAMM, L LEE · 2012 to 2016
$5.8M
Renal Function Derangements in HypertensionR01HL026371 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI NAVAR, LUIS GABRIEL · 1985 to 2010
$3.4M
Eicosanoid-Induced Vascular Growth During InjuryR01HL079109 · NHLBI · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI MALIK, KAFAIT U · 2005 to 2015
$3.3M
Superoxide and nitric Oxide Interactions in the KidneyR01HL066432 · NHLBI · TULANE UNIVERSITY OF LOUISIANA · PI MAJID, DEWAN SYED ABDUL · 2001 to 2012
$3.0M
Regulatory Mechanisms in Autoimmune ArthritisI01BX001193 · VA · MEMPHIS VA MEDICAL CENTER · PI BRAND, DAVID D. · 2013 to 2016
–
BLRD VA I01 BX001193NHLBI NIH HHS R01 HL019134NHLBI NIH HHS R01 HL026371NHLBI NIH HHS R01 HL066432NHLBI NIH HHS R01 HL079109NHLBI NIH HHS R01HL-079109-09NHLBI NIH HHS R01HL-19134-40NHLBI NIH HHS R01HL26371NHLBI NIH HHS R01HL-66432NIGMS NIH HHS P30 GM103337NIGMS NIH HHS P30GM103337
6 · The paper itself

Abstract

6β-Hydroxytestosterone, a cytochrome P450 1B1-derived metabolite of testosterone, contributes to the development of angiotensin II-induced hypertension and associated cardiovascular pathophysiology. In view of the critical role of angiotensin II in the maintenance of renal homeostasis, development of hypertension, and end-organ damage, this study was conducted to determine the contribution of 6β-hydroxytestosterone to angiotensin II actions on water consumption and renal function in male Cyp1b1(+/+) and Cyp1b1(-/-) mice. Castration of Cyp1b1(+/+) mice or Cyp1b1(-/-) gene disruption minimized the angiotensin II-induced increase in water consumption, urine output, proteinuria, and sodium excretion and decreases in urine osmolality. 6β-Hydroxytestosterone did not alter angiotensin II-induced increases in water intake, urine output, proteinuria, and sodium excretion or decreases in osmolality in Cyp1b1(+/+) mice, but restored these effects of angiotensin II in Cyp1b1(-/-) or castrated Cyp1b1(+/+) mice. Cyp1b1 gene disruption or castration prevented angiotensin II-induced renal fibrosis, oxidative stress, inflammation, urinary excretion of angiotensinogen, expression of angiotensin II type 1 receptor, and angiotensin-converting enzyme. 6β-Hydroxytestosterone did not alter angiotensin II-induced renal fibrosis, inflammation, oxidative stress, urinary excretion of angiotensinogen, expression of angiotensin II type 1 receptor, or angiotensin-converting enzyme in Cyp1b1(+/+)mice. However, in Cyp1b1(-/-) or castrated Cyp1b1(+/+) mice, it restored these effects of angiotensin II. These data indicate that 6β-hydroxytestosterone contributes to increased thirst, impairment of renal function, and end-organ injury associated with angiotensin II-induced hypertension in male mice and that cytochrome P450 1B1 could serve as a novel target for treating renal disease and hypertension in male mice.

Indexed as

Analysis of VarianceAngiotensin IIAnimalsBiopsy, NeedleCastrationCytochrome P-450 CYP1B1Disease Models, AnimalHydroxytestosteronesHypertensionImmunohistochemistryKidney DiseasesKidney Function TestsMaleMiceOxidative StressRandom Allocation6 beta-hydroxytestosteroneAngiotensin IICytochrome P-450 CYP1B1HydroxytestosteronesReactive Oxygen SpeciesRNA, Messenger6β-hydroxytestosteroneangiotensinogencytochrome P450 1B1fibrosis

Identifiers

PMID26928804
PMCPMC4833582
OpenAlexW2292644001

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.