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Reduced Nitric Oxide–cGMP Signaling Contributes to Vascular Dysfunction Induced by the Adipokine Chemerin.
Author(s) -
Neves Karla,
LOBATO NUBIA,
LOPES RHEURE,
ZANOTTO CAMILA,
FILGUEIRA FERNANDO,
OLIVEIRA ANA MARIA,
TOSTES RITA
Publication year - 2013
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.27.1_supplement.1091.6
Subject(s) - chemerin , endocrinology , adipokine , medicine , chemistry , superoxide , enos , nitric oxide , nadph oxidase , endothelial dysfunction , nitric oxide synthase , oxidative stress , biochemistry , insulin resistance , diabetes mellitus , enzyme
The new adipokine Chemerin has been implicated in the cardiovascular complications associated with obesity and metabolic syndrome. The present study was designed to test the hypothesis that the adipokine chemerin induces vascular dysfunction by decreasing nitric oxide (NO)–cGMP signaling. Isometric contraction was recorded in rat thoracic aortic rings incubated with chemerin (0.5ng/mL or 5ng/mL; 1 hour) or vehicle. Chemerin markedly reduced both sodium nitroprusside [pD 2 : 8,6±0,1 vs. chem 0,5ng/mL=7,4±0,1; chem 5ng/mL=6,9±0,1] and acetylcholine [Emax: vehicle=93,1±11,1; chem 0,5ng/mL=66,1±3,1; chem 5ng/mL= 63,8±12,6] ‐ induced relaxation in rat aorta. Chemerin increased eNOS phosphorylation [a.u.: 1 vs. 1.9±0.1], but also induced NOS uncoupling, as demonstrated by a decreased eNOS dimer/monomer ratio [a.u.: 1 vs. 0,5±0,1]. Chemerin decreased vascular expression of soluble guanylate cyclase [a.u.: 1 vs. 0.6±0.1] as well as cGMP levels [pmol/mg: 1±0,2]. Chemerin increased superoxide anion generation [rlu: 100 vs. 120,5±8,1], determined by lucigenin chemiluminescence assay in cultured VSMCs from rat aorta, an effect that was abrogated by incubation with L‐NAME [120,5 vs. 71,6±9,4] or tempol [120,5 vs. 73,3±7,5]. In conclusion, chemerin decreases NO‐cGMP signaling via ROS generation, NOS uncoupling and decreased GC activity. Our studies may contribute to a better understanding of the role of factors released by the visceral adipose tissue on vascular function and, consequently, on the vascular dysfunction in obesity and obesity‐associated diseases.