C-Reactive Protein Does Not Relax Vascular Smooth Muscle: Effects Mediated by Sodium Azide in Commercially Available Preparations H-00996-2004 R1

C-reactive protein (CRP), an acute phase protein and newly recognized indicator of cardiovascular risk, may have direct actions on the vascular wall. Previous studies suggest CRP is a vasodilator that activates smooth muscle K + channels. We examined the reported vasoactive properties of CRP and further explored mechanisms of action. CRP decreased blood pressure in rats and increased coronary flow in open-chest dogs at a constant coronary perfusion pressure. CRP relaxed rat aortic rings and mesenteric small arteries contracted with phenylephrine. Relaxation was not affected by endothelial denudation or inhibition of nitric oxide synthase but was blocked by inhibiting soluble guanylate cyclase or K + channels. CRP solutions remained effective, i.e., elicited vasodilation, even after boiling or enzymatic digestion, suggesting the presence of a non-protein contaminant. Sodium azide (NaN 3 ; 0.1%) is the preservative used for commercially available CRP and a potential source of nitric oxide (NO). NaN 3 elicited the same cardiovascular effects as CRP preparations at equal concentrations and its actions were blocked by inhibiting guanylate cyclase and K + channels. Azide-free CRP, prepared by gel filtration centrifugation and confirmed by electrophoresis, had no effect on vascular tone. Inhibition of vascular smooth muscle catalase with 3-amino-1,2,4-triazole completely prevented the effects of NaN 3 and azide-containing CRP solutions. We demonstrate that the acute vasoactive properties of commercially available CRP preparations are attributable to NaN 3 (and subsequent production of NO by catalase); therefore, the study suggests a reappraisal of the acute role of CRP in regulating vascular tone.