Abstract MP07: Endogenous Chemerin Amplifies Nerve-Dependent Arterial Contraction

Abstract

The adipokine chemerin causes contraction of isolated arteries and is implicated in blood pressure regulation, especially in the obese population that have elevated levels of circulating chemerin. Because chemerin is expressed in the perivascular adipose tissue (PVAT) that facilitates the sympathetic innervation of the blood vessel, we tested the hypothesis that chemerin (endogenous and exogenous) would amplify the effects of the sympathetic nervous system in mediating electrical field stimulated (EFS) contraction. The model was the superior mesenteric artery with PVAT, mounted into tissue baths for isometric contraction. Immunohistochemistry validated a robust expression of chemerin in the PVAT surrounding the superior mesenteric artery. EFS (0.3-20 Hz) caused a frequency-dependent, prazosin-sensitive contraction that was reduced (~40%) by the chemerin receptor ChemR23 antagonist CCX832 (100 nM; figure) but not by the inactive congener CCX826 (100 nM). Exogenous chemerin (1 μM) amplified EFS-induced contraction in a manner that was also blocked by CCX832. Chemerin did not directly modify contraction of the superior mesenteric artery (-PVAT) to cumulative concentrations of norepinephrine (1 nM - 10 μM), supporting that contractile amplification by chemerin was not at the level of smooth muscle. These studies raise the interesting possibilities that endogenous chemerin and/or ChemR23 modifies nerve-mediated contraction. This is significant because of the well appreciated role of the sympathetic nervous system in blood pressure control.