Chemerin reduces vascular nitric oxide/cGMP signalling in rat aorta: a link to vascular dysfunction in obesity?

Author(s)

Neves, Karla Bianca ^{[1, 2]} ; Lobato, Nubia S. ^[3] ; Moreira Lopes, Rheure Alves ^[2] ; Filgueira, Fernando P. ^[2] ; Zanotto, Camila Ziliotto ^[3] ; Oliveira, Ana Maria ^[1] ; Tostes, Rita C. ^[2]

Affiliation

^[1] Univ Sao Paulo, Fac Pharmaceut Sci Ribeirao Preto, Dept Chem & Phys, BR-14049 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, BR-14049 Ribeirao Preto, SP - Brazil

^[3] Univ Fed Goias, Dept Biol Sci, Jatai, Go - Brazil

• Document type: Journal article
• Source: Clinical Science; v. 127, n. 1-2, p. 111-122, JUL 2014.
• Web of Science Citations: 35

Abstract

The adipokine chemerin has been implicated in cardiovascular complications associated with obesity and the metabolic syndrome. Chemerin has direct effects on the vasculature, augmenting vascular responses to contractile stimuli. As NO/cGMP signalling plays a role in vascular dysfunction associated with obesity and the metabolic syndrome, we hypothesized that chemerin induces vascular dysfunction by decreasing NO/cGMP signalling. Aortic rings from male Wistar rats (10-12 weeks of age) were incubated with chemerin (0.5 or 5 ng/ml for 1 h) or vehicle and isometric tension was recorded. Vasorelaxation in response to ACh (acetylcholine), SNP (sodium nitroprusside) and BAY 412272 {[}an sGC (soluble guanylate cyclase) stimulator] were decreased in chemerin-treated vessels. The NOS (NO synthase) cofactor BH4 (tetrahydrobiopterin), an O-2(-) (superoxide anion) scavenger (tiron) and a SOD (superoxide dismutase) mimetic (tempol) abolished the effects of chemerin on ACh-induced vasodilation. eNOS (endothelial NOS) phosphorylation, determined by Western blotting, was increased in chemerin-treated vessels; however, the enzyme was mainly in the monomeric form, with decreased eNOS dimer/monomer ratio. Chemerin decreased the mRNA levels of the rate-limiting enzyme for BH4 biosynthesis GTP cyclohydrolase I. Chemerin-incubated vessels displayed decreased NO production, along with increased ROS (reactive oxygen species) generation. These effects were abrogated by BH4, tempol and L-NAME (N-G-nitro-L-arginine methyl ester). sGC protein expression and cGMP levels were decreased in chemerin-incubated vessels. These results demonstrate that chemerin reduces NO production, enhances NO breakdown and also decreases NO-dependent cGMP signalling, thereby reducing vascular relaxation. Potential mechanisms mediating the effects of chemerin in the vasculature include eNOS uncoupling, increased O-2(-) generation and reduced GC activity. (AU)

• FAPESP's process: 10/02434-0 - Effects of the adipokine chemerin on the vascular reactivity: analysis in rat aorta
• Grantee: Karla Bianca Neves
• Support Opportunities: Scholarships in Brazil - Master