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TNFα is central to the augmented myogenic response of skeletal muscle resistance arteries in heart failure
Author(s) -
Kroetsch Jeffrey Thomas,
Meissner Anja,
Momen Abdul,
Husain Mansoor,
Bolz SteffenSebastian
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.1026.12
Subject(s) - medicine , skeletal muscle , heart failure , tumor necrosis factor alpha , myograph , ligation , cardiology , endocrinology , artery
A hallmark of heart failure (HF) is elevated peripheral resistance, which primarily results from an augmented myogenic response (MR, the intrinsic property of resistance arteries (RA) to adapt diameter to changes in pressure). In cerebral arteries from HF mice, tumor necrosis factor α (TNFα) plays a central role for the enhancement of MRs (through activation of sphingosine kinase‐1). We hypothesized that TNFα is equally important for the augmentation of MRs in skeletal muscle RA and hence, increased peripheral resistance in HF. HF was induced in Male C57/BL6 mice through surgical ligation of the left anterior descending coronary artery. 6–8wks post‐ligation, cremaster muscle RA were isolated and cannulated on a pressure myograph. Elevations in transmural pressure (20–100mmHg in 20mmHg steps) induced MRs that were increased in RA from HF compared to sham‐operated mice (n=7). MRs were not enhanced in RA from HF TNFα −/− mice (n=5). However, treatment with the TNFα scavenger etanercept (1mg/kg 2x/wk for 6wks post‐ligation) did not block the HF‐induced increase in MRs. Our data suggest that: (i) the augmented MR in skeletal muscle arteries contributes to increased vascular resistance in HF, (ii) TNFα is a mandatory component of this response, and (iii) chronic scavenging of TNFα might be compensated by redundant organization of MR signaling pathways. Funding: NSERC, HSFO, and CIHR