HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 288/4/H1786    most recent 00996.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (33) Citing Articles via Google Scholar Google Scholar Articles by Swafford, A. N. Articles by Dick, G. M. Search for Related Content PubMed PubMed Citation Articles by Swafford, A. N., Jr. Articles by Dick, G. M.

C-reactive protein does not relax vascular smooth muscle: effects mediated by sodium azide in commercially available preparations

Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana

Submitted 27 September 2004 ; accepted in final form 18 November 2004

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.

catalase; nitric oxide; soluble guanylate cyclase; potassium channel; guanosine 3',5'-cyclic monophosphate

This article has been cited by other articles:

				G. M. Dick, I. N. Bratz, L. Borbouse, G. A. Payne, U. D. Dincer, J. D. Knudson, P. A. Rogers, and J. D. Tune Voltage-dependent K+ channels regulate the duration of reactive hyperemia in the canine coronary circulation Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H2371 - H2381. [Abstract] [Full Text] [PDF]

				T. Kuji, T. Masaki, L. Li, and A. K. Cheung Expression of C-reactive protein in myointimal hyperplasia in a porcine arteriovenous graft model Nephrol. Dial. Transplant., September 1, 2007; 22(9): 2469 - 2475. [Abstract] [Full Text] [PDF]

				E. Grad, M. Golomb, I. Mor-Yosef, N. Koroukhov, C. Lotan, E. R. Edelman, and H. D. Danenberg Transgenic expression of human C-reactive protein suppresses endothelial nitric oxide synthase expression and bioactivity after vascular injury Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H489 - H495. [Abstract] [Full Text] [PDF]

				R. Schwartz, S. Osborne-Lawrence, L. Hahner, L. L. Gibson, A. K. Gormley, W. Vongpatanasin, W. Zhu, R. A. Word, D. Seetharam, S. Black, et al. C-Reactive Protein Downregulates Endothelial NO Synthase and Attenuates Reendothelialization In Vivo in Mice Circ. Res., May 25, 2007; 100(10): 1452 - 1459. [Abstract] [Full Text] [PDF]

				Y. Zhong, S.-H. Li, S.-M. Liu, P. E. Szmitko, X.-Q. He, P. W.M. Fedak, and S. Verma C-Reactive Protein Upregulates Receptor for Advanced Glycation End Products Expression in Human Endothelial Cells Hypertension, September 1, 2006; 48(3): 504 - 511. [Abstract] [Full Text] [PDF]

				J. P Casas, T. Shah, J. Cooper, E. Hawe, A. D McMahon, D. Gaffney, C. J Packard, D. S O'Reilly, I. Juhan-Vague, J. S Yudkin, et al. Insight into the nature of the CRP-coronary event association using Mendelian randomization Int. J. Epidemiol., August 1, 2006; 35(4): 922 - 931. [Abstract] [Full Text] [PDF]

				E. Paffen and M. P.M. deMaat C-reactive protein in atherosclerosis: A causal factor? Cardiovasc Res, July 1, 2006; 71(1): 30 - 39. [Abstract] [Full Text] [PDF]

				G. Doronzo, I. Russo, M. Trovati, and G. Anfossi Sodium azide in commercially available C-reactive protein preparations does not influence matrix metalloproteinase-2 synthesis and release in cultured human aortic vascular smooth muscle cells. Clin. Chem., June 1, 2006; 52(6): 1200 - 1201. [Full Text] [PDF]

				M. Oroszlan, E. Herczenik, S. Rugonfalvi-Kiss, A. Roos, A. J Nauta, M. R Daha, I. Gombos, I. Karadi, L. Romics, Z. Prohaszka, et al. Proinflammatory changes in human umbilical cord vein endothelial cells can be induced neither by native nor by modified CRP Int. Immunol., June 1, 2006; 18(6): 871 - 878. [Abstract] [Full Text] [PDF]

				A. Tedgui and Z. Mallat Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways Physiol Rev, April 1, 2006; 86(2): 515 - 581. [Abstract] [Full Text] [PDF]

				E. Qamirani, H. M. Razavi, X. Wu, M. J. Davis, L. Kuo, and T. W. Hein Sodium azide dilates coronary arterioles via activation of inward rectifier K+ channels and Na+-K+-ATPase Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1617 - H1623. [Abstract] [Full Text] [PDF]

				M. B. Pepys, P. N. Hawkins, M. C. Kahan, G. A. Tennent, J. R. Gallimore, D. Graham, C. A. Sabin, A. Zychlinsky, and J. de Diego Proinflammatory Effects of Bacterial Recombinant Human C-Reactive Protein Are Caused by Contamination With Bacterial Products, Not by C-Reactive Protein Itself Circ. Res., November 25, 2005; 97(11): e97 - e103. [Abstract] [Full Text] [PDF]

				C. Liu, S. Wang, A. Deb, K. A. Nath, Z. S. Katusic, J. P. McConnell, and N. M. Caplice Proapoptotic, Antimigratory, Antiproliferative, and Antiangiogenic Effects of Commercial C-Reactive Protein on Various Human Endothelial Cell Types In Vitro: Implications of Contaminating Presence of Sodium Azide in Commercial Preparation Circ. Res., July 22, 2005; 97(2): 135 - 143. [Abstract] [Full Text] [PDF]

				C. W. van den Berg and K. E. Taylor Letter to the Editor: Letter in Response to Bisoendial et al: "Activation of Inflammation and Coagulation After Infusion of C-Reactive Protein in Humans" Circ. Res., July 8, 2005; 97(1): e2 - e2. [Full Text] [PDF]