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Role of 20‐HETE in Differential Effects of High Salt Diet on Resistance Artery Function in Dahl Salt‐Sensitive (SS) Rats and SS‐5BN Consomic Rats
Author(s) -
Beehner Kathleen,
Falck John R.,
Roman Richard J.,
Lombard Julian H.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.976.6
Subject(s) - myograph , endocrinology , medicine , vasodilation , chemistry , hypoxia (environmental) , enzyme , acetylcholine , biology , biochemistry , oxygen , organic chemistry
This study tested the hypothesis that an increased production of 20‐hydroxyeicosatetraenoic acid (20‐HETE) by cytochrome P450‐4A ω‐hydroxylase (CYP4A) enzymes and/or an enhanced sensitivity to 20‐HETE contributes to impaired vascular relaxation in Dahl salt‐sensitive (SS) rats. The role of 20‐HETE in modulating vessel responses was assessed by comparing vascular relaxation to reduced PO 2 and acetylcholine (ACh) in pressurized middle cerebral arteries of SS rats vs. consomic SS‐Chr 5 BN /Mcwi (SS‐5 BN ) rats having CYP4A genes from chromosome 5 of the Brown Norway rat introgressed onto the SS genetic background. Compared to SS‐5 BN rats, vasodilator responses to ACh and hypoxia were impaired in SS rats fed either low salt (LS; 0.4% NaCl) or high salt (HS; 4% NaCl) diet. Vascular relaxation in SS rats could be restored to levels comparable to those in the SS‐5 BN rats by inhibiting CYP4A enzymes with dibromododecenyl methylsulfimide (DDMS; 50 μM). In wire myograph studies, mesenteric arteries of SS rats fed HS diet for 3 days or 3 weeks also exhibited an enhanced response to the 20‐HETE agonist 20–5,14‐HEDE (WIT003) compared to SS rats fed LS diet and SS‐5 BN rats fed either HS or LS diet. These findings suggest that alterations in 20‐HETE synthesis and/or sensitivity contribute to salt‐induced alterations in vascular function in SS rats (NIH #HL65289, #HL72920, #HL92026; #DK‐38226: #T32 HL007852).