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Role of increased oxidative stress and cytochrome P450‐4A ω‐hydroxylase (CYP450‐4A) metabolites in contributing to salt‐induced loss of arteriolar dilation in the hamster cheek pouch
Author(s) -
Lombard Julian H.,
Balus Sarah F.,
Buelow Matthew W.
Publication year - 2006
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.20.4.a268-b
Subject(s) - cheek pouch , chemistry , sodium nitroprusside , endocrinology , medicine , oxidative stress , arteriole , microcirculation , vasodilation , hamster , anatomy , nitric oxide , biochemistry , biology
This study investigated the mechanisms by which high salt (HS) diet impairs NO‐dependent vascular relaxation in arterioles of the hamster cheek pouch. Golden hamsters were fed a low salt (LS) (0.4% NaCl) diet or switched to a HS diet (4.0% NaCl) for 3–6 days. The animals were anesthetized with pentobarbital and diameters of third order arterioles of the cheek pouch microcirculation were measured via television microscopy. The pouch was continuously superfused with physiological salt solution and concentration‐response curves were determined for the endothelium‐dependent dilator acetylcholine (ACh) and the NO donor sodium nitroprusside (SNP). HS diet eliminated arteriolar dilation to ACh and SNP, without affecting blood pressure. Maximal dilation of arterioles to 1 mM adenosine was similar in animals on HS and LS diet. Arteriolar dilation to ACh and SNP in animals on HS diet was restored by addition of tempol to the drinking water to scavenge superoxide radicals or by addition of dibromo‐dodecenyl‐methylsulfimide (DDMS) to the superfusion solution to inhibit cytochrome P450‐4A (CYP‐450 4A) ω‐hydroxylase. Combined treatment with tempol and DDMS had no additional effect on arteriolar dilation. These results suggest that increased oxidative stress and CYP450‐4A metabolites contribute to impaired NO‐dependent dilation of arterioles during elevated dietary salt intake [NIH #HL‐29587, HL‐65289 and HL‐72920].