Determination of Role of Endothelium in Vasoactive Effect of CRP

Objective—C-reactive protein (CRP) is a sensitive marker of inflammation and a prognostic marker in cardiovascular disease. Evidence suggests direct biological activities of CRP within the vascular wall. The study was designed to examine the vasoreactive effects of CRP. Methods and Results—Human internal mammary artery rings were obtained during cardiovascular bypass surgery and suspended in an organ bath chamber. The rings were precontracted with endothelin-1, and response to cumulative concentrations of CRP was obtained. Experiments were repeated after initial incubation with 20, 40, and 60 mmol/L KCl, the potassium channel blockers BaCl, tetraethylammonium chloride, and glibenclamide, and the NO synthase inhibitor N-monomethyl-L-arginine and also after removal of the endothelium. CRP caused dose-dependent relaxation of human internal mammary artery rings, which was not affected by preincubation with N-monomethyl-L-arginine or removal of the endothelium. Maximum relaxation response to CRP (79.5 10%) was attenuated by KCl (2.5 11.5%, P 0.001), BaCl (24.5 7.5%, P 0.001), and tetraethylammonium chloride (34.9 8.25%, P 0.01) but not by glibenclamide. Conclusions–The present study demonstrates that CRP exerts an endothelium-independent vasorelaxing effect via potassium channels. Thus, the study suggests a role of CRP in the regulation of vascular tone. (Arterioscler Thromb Vasc Biol. 2002;22:1865-1868.)

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