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EDHF prevents endothelial dysfunction in response to a high‐fat diet in the Wistar rat
Author(s) -
Azevedo Stefanie M.,
Menicucci Steve D.,
Naik Jay S.
Publication year - 2008
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.22.1_supplement.732.3
Subject(s) - endocrinology , medicine , vasodilation , mesenteric arteries , phenylephrine , bradykinin , endothelium derived hyperpolarizing factor , electrical impedance myography , nitric oxide , endothelium , acetylcholine , endothelial dysfunction , vasoconstriction , blood pressure , artery , receptor , charybdotoxin
Individuals consuming a high‐fat diet, often display reduced responsiveness to endothelial‐dependant vasodilators such as acetylcholine or bradykinin. Endothelium‐derived hyperpolarizing factor (EDHF) may be an important vasoactive factor in resistance arteries from many vascular beds. However, its importance relative to other endothelial derived relaxing factors such as nitric oxide and prostaglandins is unclear. Although, genetic models of obesity and type II diabetes have demonstrated that EDHF‐mediated vasodilation is impaired; it is unknown if EDHF function is also affected by a high‐fat diet. 3–4 wk old Male Wistar rats were fed either a high‐fat diet (60% lard) or chow for 10–11 wks. Isolated small mesenteric arteries were pre‐constricted with Phenylephrine (PE; 10 −9 – 10 −5 M) and administered acetylcholine (ACh; 10 −8 – 10 −6 M) in the presence of either vehicle or Indomethacin (10 μm) and N(ω)‐nitro‐L‐arginine (L‐NNA; 100 μm). Vasoconstrictor responses to PE were also assessed in a separate set of untreated arteries. Blood pressure was determined by tail‐cuff. Body and epididymal fat pad weight were significantly greater in fat‐fed rats compared to chow fed. Mean arterial blood pressure was not different between groups. ACh‐induced dilation in arteries treated with vehicle was similar between chow and fat‐fed rats. Pre‐treating arteries with Indomethacin and L‐NNA blunted ACh‐mediated vasodilation in chow fed rats but did not alter ACh responses in arteries from fat‐fed animals. Reactivity to PE was not different between groups. These results suggest that role for EDHF in ACh‐mediated vasodilation is enhanced in small mesenteric arteries following a high‐fat diet.