Premium
Angiotensin II‐Induced Vasoconstriction in Skeletal Muscle: Effects of Aging and TNF‐α
Author(s) -
Behnke Bradley Jon,
Dominguez James M,
Park Yoonjung,
Delp Michael D
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.775.2
Subject(s) - vasoconstriction , proinflammatory cytokine , medicine , angiotensin ii , endocrinology , vasodilation , tumor necrosis factor alpha , vascular smooth muscle , inflammation , receptor , endothelial dysfunction , angiotensin receptor , oxidative stress , smooth muscle
There is increasing evidence that oxidative stress and vascular inflammation contribute to old‐age associated vascular dysfunction. With advancing age there are elevated levels of tumor necrosis factor (TNF)‐α, which, via endothelial vasodilator impairment, may exacerbate the vasoconstrictor responses of angiotensin (ANG)‐II. Purpose To determine whether the proinflammatory cytokine TNF‐α contributes to alterations in ANG II‐mediated vasoconstriction with aging. Methods Pegylated soluble human TNF type 1 receptor (PEG sTNF‐RI; Amgen Inc) was administered (1 mg/kg, s.c., 3x/wk) for 10 wks in eight young (4–6 mo) and seven old (22–24 mo) male Fischer 344 rats to inhibit soluble TNF‐α binding to receptors. At the end of the TNF‐α inhibition period, gastrocnemius muscle arterioles were isolated and concentration response relations to the cumulative addition of ANG II (3x10 −12 to 3x10 −5 M) were determined. Results Chronic TNF‐α inhibition significantly diminished the vasoconstrictor response of arterioles from ~ 60% vasoconstriction in the old untreated animals to ~ 40% in the old treated animals. Furthermore, age‐associated differences (young vs. old) in ANG II mediated vasoconstriction were eliminated with the chronic TNF‐α inhibition. Conclusion With old age there is an enhanced vasoconstriction to ANG II which is due, in part, to diminished endothelial function. Chronic TNF‐α inhibition eliminated age‐related differences in ANG II induced vasoconstriction which suggests that the impaired NOS signaling pathway linked to ANG II receptors with old age may be the result of a proinflammatory state.