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Attenuated Rapid‐Onset Vasodilation with Greater Force Production in Skeletal Muscle of Caveolin‐2 −/− Mice
Author(s) -
Fernando Charmain,
Liu Yajun,
Sowa Greg,
Segal Steven
Publication year - 2016
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.30.1_supplement.945.2
Subject(s) - endocrinology , vasodilation , medicine , acetylcholine , skeletal muscle , microcirculation , chemistry , caveolae , blood vessel , contraction (grammar) , endothelium , nitric oxide , myogenic contraction , nitric oxide synthase , constriction , circulatory system , anatomy , biology , smooth muscle , biochemistry , cell
Caveolin‐2 (Cav2) is a major protein component in caveolae, minute invaginations in plasma membranes of endothelial cells. While absence of Cav2 increases pulmonary endothelial cell proliferation and inhibits tumor growth (PMC133690; PMC4233177), the role of Cav2 in the microcirculation of skeletal muscle is unknown. We tested the hypothesis that genetic deletion of Cav2 would alter the reactivity of microvascular resistance networks controlling muscle blood flow. Internal diameter (ID) responses to physiological agonists and to contractile activity were studied at 35°C in the left gluteus maximus muscle (GM) of anesthetized Cav2 −/− and littermate wild‐type (WT) mice (n=5 males/group; 6 months old). For feed arteries (FA), first‐ (1A), second‐ (2A) and third‐order (3A) arterioles, resting IDs (means: 45, 35, 25, 12 μm) and maximal IDs (65, 55, 45, 30 μm) were not different between groups, nor were cumulative endothelium‐dependent dilations to acetylcholine (ACh, 10 −9 –10 −5 M); all right‐shifted ~1 log unit during nitric oxide synthase inhibition (L‐NAME, 10 −4 M). Constriction‐response curves to norepinephrine (NE, 10 −9 –10 −5 M) overlapped for respective vessel branches. During twitch contractions (2 & 4 Hz; 30 s), steady‐state dilations (range, 5–20 μm) were again similar between groups. However, for single maximal tetanic contractions (100 Hz; 100, 250 & 500 ms), rapid onset vasodilation (ROV) increased with contraction duration but was reduced by 20–50% across vessel branches of Cav2 −/− vs. WT (P<0.05). Remarkably, maximal force production (mN/mm 2 ) was ~40% greater in Cav2 −/− (152 ± 14) vs. WT (110 ± 3). Thus, while microvascular reactivity is maintained to ACh, NE and moderate contractile activity, diminished ROV with enhanced force production reveals a novel phenotype for Cav2 deletion in mouse skeletal muscle Support or Funding Information NIH R37‐HL041026