Chemerin reduces vascular nitric oxide - cyclic guanosine monophosphate signaling: a link to vascular dysfunction in obesity?

The adipokine chemerin has been implicated in cardiovascular complications associated with obesity and metabolic syndrome. Chemerin has direct effects in the vasculature, augmenting vascular responses to contractile stimuli. Since nitric oxide (NO)–cyclic guanosine monophosphate (cGMP) signaling plays a role in vascular dysfunction associated with obesity and metabolic syndrome, we hypothesized that chemerin induces vascular dysfunction by decreasing NO-cGMP signaling. Aortic rings from male Wistar rats (10-12 weeks-old) were incubated with chemerin (0.5 ng/mL or 5 ng/mL, 1 hour) or vehicle, and isometric tension was recorded. Vasorelaxation to acetylcholine (ACh), sodium nitroprusside and BAY 412272 [a soluble guanylate cyclase (sGC) stimulator] were decreased in chemerin-treated vessels. The NO synthase cofactor tetrahydrobiopterin (BH4), a superoxide anion (O2-) scavenger (tiron) and a superoxide dismutase mimetic (tempol) abolished chemerin effects on ACh-induced vasodilation. eNOS 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 reactive oxygen species generation. These effects were abrogated by BH4, tempol and L-NAME. sGC protein expression an...
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research