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Effects of the sirtuin inhibitor, salermide, on exercise‐induced changes in endothelial function
Author(s) -
Olesiak Matthew,
Hoffman Rebecka M.,
Harris M. Brennan
Publication year - 2011
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.25.1_supplement.1108.14
Subject(s) - phenylephrine , sodium nitroprusside , medicine , vasodilation , endocrinology , acetylcholine , sed , chemistry , endothelium , endothelial dysfunction , enos , nitric oxide , nitric oxide synthase , blood pressure
SIRT1 has been identified as a regulator of eNOS and endothelial function; however, no studies have examined the role of SIRT1 in exercise‐induced changes in endothelial function. We investigated the effects of the novel SIRT1 inhibitor, salermide, on vascular reactivity in rat aortas and femoral arteries following exercise training of different durations. Male, Wistar rats (8–9 mo old) were divided into four groups (n=10/group); sedentary (SED), 1‐day exercise (1D), 2‐weeks exercise (2WK) or 6 weeks exercise (6WK). Exercise consisted of running on a motor‐driven treadmill at 15 m/min, 15% grade for 40 min (1D) or increased up to 1 h at the end of 2 weeks (2WK) and sustained for an additional 4 weeks (6WK). Vascular reactivity was examined by constructing dose response curves to phenylephrine (PE, 10 −7 ‐10 −4 M), sodium nitroprusside (SNP, 10 −8 ‐10 −5 M), and acetylcholine (ACh, 10 −7 ‐3×10 −5 M) in the presence or absence of salermide (30 μM). Salermide significantly ( P <0.05) impaired Ach‐induced vasorelaxation in both aortas and femoral arteries in all groups. In addition, the reduction in maximal Ach‐induced relaxation due to salermide was significantly greater ( P <0.05) in 1D vs SED, 2WK and 6WK. In conclusion, these data suggest that SIRT1 plays an important role in endothelium dependent vasodilation and is especially important following 1 bout of acute exercise. Supported by the Jeffress Memorial Trust (MBH).