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High fat feeding alters vasoconstrictor responsiveness in rat skeletal muscle by increasing inducible nitric oxide synthase activity
Author(s) -
Richards Stephen Michael,
Bussey Carol T,
Keske Michelle A,
Rattigan Stephen
Publication year - 2012
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.26.1_supplement.869.3
Subject(s) - medicine , endocrinology , vasoconstriction , insulin resistance , nitric oxide synthase , nitric oxide , insulin , glucose homeostasis , chemistry , vasodilation , biology
In insulin resistance endothelin‐1 (ET‐1) levels are consistently increased, but opinion is divided whether ET‐1 vasoconstrictor responsiveness is enhanced or impaired. We examined vascular responses to ET‐1 in rats made insulin resistant by high fat feeding, using the isolated, pump‐perfused hindlimb. Male Sprague‐Dawley rats were fed a high‐fat diet for 4 weeks, resulting in an 81% increase in epididymal fat pad weight, accompanied by increased fasting plasma insulin, but not glucose. Vasoconstriction by ET‐1 (1 or 3nM) was reduced by the high‐fat diet. Treatment with the nitric oxide (NO) synthase inhibitor N G ‐nitro‐L‐arginine methyl ester (L‐NAME) significantly increased ET‐1 vasoconstriction in both normal and high‐fat fed animals to the same level. In the presence of 1400W, a specific inhibitor of the inducible NOS (iNOS) isoform, ET‐1 reactivity in high‐fat fed rats was restored to that of rats on normal chow. These findings support the notion that high fat feeding increases muscle iNOS activity, which opposes ET‐1 vasoconstriction. The increased NO bioavailability is likely to alter the balance between constriction and dilation in insulin resistance, contributing to the impaired endothelial function commonly observed.