TY - JOUR
T1 - C-reactive protein does not relax vascular smooth muscle
T2 - Effects mediated by sodium azide in commercially available preparations
AU - Swafford, Albert N.
AU - Bratz, Ian N.
AU - Knudson, Jarrod D.
AU - Rogers, Paul A.
AU - Timmerman, Jennifer M.
AU - Tune, Johnathan D.
AU - Dick, Gregory M.
PY - 2005/4
Y1 - 2005/4
N2 - 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 that CRP is a vasodilator that activates smooth muscle K+ channels. We examined the reported vasoactive properties of CRP and further explored its 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 that were contracted with phenylephrine. Relaxation was not affected by endothelial denudation or inhibition of nitric oxide (NO) synthase but was blocked by inhibition of soluble guanylate cyclase or K+ channels. CRP solutions remained effective, i.e., elicited vasodilation, even after boiling or enzymatic digestion, which suggests the presence of a nonprotein contaminant. Sodium azide (NaN3, 0.1%) is the preservative used for commercially available CRP and a potential source of NO. NaN3 elicited the same cardiovascular effects as CRP preparations at equal concentrations, and its actions were blocked by inhibition of guanylate cyclase and K+ channels. NaN3-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 NaN3 and NaN3- containing CRP solutions. We demonstrate that the acute vasoactive properties of commercially available CRP preparations are attributable to NaN3 (and subsequent production of NO by catalase); therefore, this study suggests a reappraisal of the acute role of CRP in regulating vascular tone.
AB - 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 that CRP is a vasodilator that activates smooth muscle K+ channels. We examined the reported vasoactive properties of CRP and further explored its 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 that were contracted with phenylephrine. Relaxation was not affected by endothelial denudation or inhibition of nitric oxide (NO) synthase but was blocked by inhibition of soluble guanylate cyclase or K+ channels. CRP solutions remained effective, i.e., elicited vasodilation, even after boiling or enzymatic digestion, which suggests the presence of a nonprotein contaminant. Sodium azide (NaN3, 0.1%) is the preservative used for commercially available CRP and a potential source of NO. NaN3 elicited the same cardiovascular effects as CRP preparations at equal concentrations, and its actions were blocked by inhibition of guanylate cyclase and K+ channels. NaN3-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 NaN3 and NaN3- containing CRP solutions. We demonstrate that the acute vasoactive properties of commercially available CRP preparations are attributable to NaN3 (and subsequent production of NO by catalase); therefore, this study suggests a reappraisal of the acute role of CRP in regulating vascular tone.
KW - Catalase
KW - Guanosine 3′,5′-cyclic monophosphate
KW - Nitric oxide
KW - Potassium channel
KW - Soluble guanylate cyclase
UR - http://www.scopus.com/inward/record.url?scp=15744364686&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.00996.2004
DO - 10.1152/ajpheart.00996.2004
M3 - Article
C2 - 15563529
AN - SCOPUS:15744364686
SN - 0363-6135
VL - 288
SP - H1786-H1795
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 4 57-4
ER -