Role of vascular reactive oxygen species in regulating cytochrome P450-4A enzyme expression in Dahl salt-sensitive rats.

Autor: Lukaszewicz KM; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA., Paudyal MP; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA., Falck JR; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA., Lombard JH; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA. jlombard@mcw.edu.
Jazyk: angličtina
Zdroj: Microcirculation (New York, N.Y. : 1994) [Microcirculation] 2016 Oct; Vol. 23 (7), pp. 540-548.
DOI: 10.1111/micc.12304
Abstrakt: Objective: The potential contribution of CYP4A enzymes to endothelial dysfunction in Dahl salt-sensitive rats was determined by comparison to SS-5 BN consomic rats having chromosome 5 carrying CYP4A alleles from the BN rat introgressed into the SS genetic background.
Methods: The following experiments were performed in cerebral arteries from HS-fed SS and SS-5 BN rats ± the SOD inhibitor DETC and/or the superoxide scavenger Tempol: (i) endothelial function was determined via video microscopy ± acute addition of the CYP4A inhibitor DDMS or Tempol; (ii) vascular oxidative stress was assessed with DHE fluorescence ± acute addition of DDMS, l-NAME, or PEG-SOD; and (iii) CYP4A protein levels were compared by western blotting.
Results: In DETC-treated SS-5 BN and HS-fed SS rats, (i) DDMS or Tempol ameliorated vascular dysfunction, (ii) DDMS reduced vascular oxidative stress to control levels, (iii) chronic Tempol treatment reduced vascular CYP4A protein expression, and (iv) combined treatment with Tempol and l-NAME prevented the reduction in CYP4A protein expression in MCA of HS-fed SS rats.
Conclusion: The CYP4A pathway plays a role in vascular dysfunction in SS rats and there appears to be a direct role of reduced NO availability due to salt-induced oxidant stress in upregulating CYP4A enzyme expression.
Competing Interests: Declarations of Interest: The authors have no declarations of interest to disclose.
(© 2016 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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