C-reactive protein relaxes human vessels in vitro

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.