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Alterations to Venular Function in Skeletal Muscle with Metabolic Syndrome
Author(s) -
Lemaster Kent,
Farid Zahra,
Jackson Dwayne,
Goldman Daniel,
Brock Robert,
Frisbee Jefferson
Publication year - 2017
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.31.1_supplement.683.2
Subject(s) - dilator , cremaster muscle , medicine , endocrinology , microcirculation , skeletal muscle , venule , stimulation , vasodilation , intravital microscopy , arteriole , chemistry
While the overwhelming majority of research into vascular outcomes of the metabolic syndrome have focused on the arterial/arteriolar and capillary levels, investigation into venular function and how development of metabolic syndrome impacts responses has received little attention. Using the in situ cremaster muscle of obese Zucker rats (OZR) as compared to control leans (LZR), we determined indices of venular network structure as well as vessel structure and function. At ~17 weeks of age, skeletal muscle post‐capillary venular density was reduced by ~20% in LZR vs. OZR, although there was no evidence of remodeling of the wall of individual venules impacting passive diameter. Initial basal diameter and blood flow within individual venules of ~25 mm and ~ 60 mm diameter was similar between LZR and OZR, although an increased variability was evident. Dilator responses to acetylcholine were consistently blunted in venules of OZR vs. LZR, and this reflected multiple effects: including an oxidant stress‐based loss of venular nitric oxide bioavailability, an increased constrictor tone from TxA 2 and an increased constrictor tone mediated via the α 1 adrenergic receptor. Impaired dilator responses were also coupled to vessels where increased leukocyte adhesion/rolling was clearly present. Venular constrictor responses between LZR and OZR were comparable for angiotensin II, endothelin and α 2 adrenoreceptor stimulation, although responses to α 1 adrenoreceptor stimulation were mildly elevated, but with increased variability. In response to field stimulation of the cremaster muscle (0.5 or 1/s, 400 ms duration, 60 Hz within train, 7V), venular dilator and hyperemic responses to contraction were blunted in OZR vs. LZR, but responses at the higher frequency were similar in magnitude. These results suggest that alterations in venular function may contribute to dysregulation of flow distribution in skeletal muscle with metabolic syndrome and impair parameters of mass transport and exchange. Support or Funding Information National Institutes of Health; American Heart Association