title: C-reactive protein does not relax vascular smooth muscle: effects mediated by sodium azide in commercially available preparations.
abstract: 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 (NaN(3), 0.1%) is the preservative used for commercially available CRP and a potential source of NO. NaN(3) elicited the same cardiovascular effects as CRP preparations at equal concentrations, and its actions were blocked by inhibition of guanylate cyclase and K(+) channels. NaN(3)-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 NaN(3)-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, this study suggests a reappraisal of the acute role of CRP in regulating vascular tone.
authors.affiliation: Department of Physiology, Louisiana State University Health Sciences Center, 1901 Perdido St., New Orleans, LA 70112, USA.
authors.forename: Albert N
authors.initials: AN
authors.lastname: Swafford
authors.forename: Ian N
authors.initials: IN
authors.lastname: Bratz
authors.forename: Jarrod D
authors.initials: JD
authors.lastname: Knudson
authors.forename: Paul A
authors.initials: PA
authors.lastname: Rogers
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Timmerman
authors.forename: Johnathan D
authors.initials: JD
authors.lastname: Tune
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Dick
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002097:C-Reactive Protein / Q000494:pharmacology*; D002374:Catalase / Q000037:antagonists & inhibitors / Q000378:metabolism; D004285:Dogs; D004347:Drug Interactions; D004734:Energy Metabolism / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019810:Sodium Azide / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D002097:C-Reactive Protein; D019810:Sodium Azide; D002374:Catalase