Role of Vascular Chemerin as a Regulator of Blood Pressure and Contributor to Cardiovascular Disease (additional)

Researchers investigated the role of the adipokine chemerin in modulating vascular function, focusing on its capacity to amplify sympathetic nerve-mediated arterial contraction and the implications for blood pressure regulation. Using isolated rat superior mesenteric arteries with and without surrounding perivascular adipose tissue (PVAT), the study combined immunohistochemistry, electrical field stimulation (EFS), pharmacological antagonists, and exogenous chemerin application to test the hypothesis that chemerin, expressed robustly in PVAT, enhances sympathetic-mediated contraction via the chemerin receptor ChemR23. Immunohistochemical analysis validated strong chemerin expression in PVAT and supported colocalization of ChemR23 with the sympathetic nerve marker tyrosine hydroxylase in PVAT, and to a lesser degree in arteries and veins, suggesting a local interface between chemerin signaling and sympathetic innervation. Functional experiments demonstrated that EFS produced frequency-dependent contractions that were reduced by the ChemR23 antagonist CCX832 (100 nM) only in arteries with intact PVAT, whereas the inactive congener CCX826 (100 nM) had no effect. Exogenous chemerin-9 (1 μM) amplified EFS-induced contractions in arteries both with and without PVAT; this amplification was blocked by CCX832 and by the α-adrenergic receptor antagonist prazosin, indicating that chemerin's potentiation of contraction is mediated through ChemR23 and requires α-adrenergic signaling.

Notably, CCX832 did not directly inhibit norepinephrine-induced contraction, nor did chemerin directly amplify norepinephrine responses, supporting the interpretation that chemerin acts by modulating sympathetic nerve-mediated neurotransmission rather than by directly enhancing smooth muscle responsiveness to norepinephrine. Additional experiments showed that endogenous activation of ChemR23 contributes to EFS-induced contraction: CCX832 alone reduced EFS responses in arteries with PVAT but not in arteries without PVAT, while CCX826 was ineffective after incubation. Together, these findings support a model in which chemerin produced in perivascular adipose tissue acts on ChemR23 receptors associated with sympathetic nerves to amplify nerve-mediated vasoconstriction. Given the central role of sympathetic nervous system activity in blood pressure control, Watts and colleagues' work implicates vascular chemerin as a potential regulator of blood pressure and a contributor to cardiovascular disease, particularly in conditions with elevated circulating chemerin such as obesity. The study highlights ChemR23 and the chemerin signaling axis in PVAT as important targets for understanding and potentially modulating sympathetic-driven vascular tone and blood pressure regulation.