Role of vascular reactive oxygen species in regulating cytochrome P450-4A enzyme expression in Dahl salt-sensitive rats. Microcirculation 2016 Oct;23(7):540-548
Date
10/28/2016Pubmed ID
27537772Pubmed Central ID
PMC5083157DOI
10.1111/micc.12304Scopus ID
2-s2.0-84992643512 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
OBJECTIVE: The potential contribution of CYP4A enzymes to endothelial dysfunction in Dahl salt-sensitive rats was determined by comparison to SS-5BN 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-5BN 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-5BN 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.
Author List
Lukaszewicz KM, Paudyal MP, Falck JR, Lombard JHMESH terms used to index this publication - Major topics in bold
AnimalsBlood Vessels
Cerebral Arteries
Cytochrome P-450 CYP4A
Endothelium, Vascular
Gene Expression Regulation, Enzymologic
Nitric Oxide
Oxidative Stress
Rats
Rats, Inbred BN
Rats, Inbred Dahl
Reactive Oxygen Species
Sodium Chloride, Dietary
Up-Regulation
