Abstract 659: Chemerin Connects Fat to Blood Pressure

Obesity and hypertension have become comorbid in near epidemic proportion, yet their biological connection is still largely a mystery. We hypothesized that the peptide chemerin (TIG2) is a candidate for connecting fat deposits (both perivascular and visceral) to elevated blood pressure. The normal Sprague Dawley or deoxycorticosterone acetate salt (DOCA) rat was used as the model. Real time RT-PCR demonstrated that chemerin was synthesized in periadventitial fat (PVAT) around the aorta. Immunohistochemical experiments showed that the primary receptor for chemerin, ChemR23, was expressed in the tunica media and endothelial layer and not in resident inflammatory cells of the artery. The potent analog chemerin-9 (1 nM — 3 uM) caused a concentration-dependent isometric contraction in isolated aorta and superior mesenteric artery that was modest in tissues at baseline [∼6-11% phenylephrine (PE) maximum contraction] but significantly amplified in the presence of the nitric oxide synthase inhibitor nitro-L-arginine (LNNA; 2.5 fold increase in maximum), endothelial removal (5.95 fold increase) or agonist-induced tone (3.2 fold increase). Chemerin-induced contraction in tissues incubated with LNNA was concentration-dependently antagonized by the novel ChemR23 antagonist CCX832, demonstrating a new role for ChemR23. Arteries from the DOCA-salt hypertensive rat demonstrated endothelial dysfunction, and chemerin-induced maximum contraction from baseline was markedly increased in the aorta (DOCA = 16+3.6%, Sham = 6.7 + 2.2% PE contraction) and superior mesenteric artery (DOCA=57.9+12.8, Sham = 11.2+2.9 % PE contraction; p<0.05). These data support a new role for chemerin as a vasoactive substance and a potential connector of the biological activity of the adipose tissue and liver (sources of chemerin) to blood pressure regulation, especially in conditions of endothelial dysfunction.