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T. Nagaoka, L. Kuo, A. Yoshida, T. W. Hein; C-reactive Protein Inhibits Endothelium-Dependent Nitric Oxide-Mediated Dilation of Isolated Porcine Retinal Arterioles. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2271.
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Elevated levels of C-reactive protein (CRP), a proinflammatory marker, are associated with systemic vascular disorders. In addition, some clinical studies have reported that elevated CRP level is an independent risk factor for ocular vascular disorders, such as diabetic retinopathy and age-related macular degeneration. However, the direct effect of CRP on ocular microvascular reactivity remains unknown. Herein, we examined whether CRP can modulate endothelium-dependent nitric oxide (NO)-mediated dilation of retinal arterioles and whether oxidative stress and Rho/Rho-kinase signaling pathways are involved in the CRP-mediated effect.
Porcine retinal arterioles (71±2 µm internal diameter) were isolated and pressurized without flow for in vitro study. Videomicroscopic techniques were employed to record diameter change.
Intraluminal treatment with a clinically relevant concentration of CRP (7 µg/mL; 1 hour) significantly attenuated dilation to endothelium-dependent nitric oxide (NO)-mediated agonist bradykinin but not to endothelium-independent NO donor sodium nitroprusside. In the presence of superoxide scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), NAD(P)H oxidase inhibitor apocynin, 3-hydroxy-3-methylglutaryl coenzyme A reductase/Rho inhibitor simvastatin or Rho-kinase inhibitor Y-27632, the detrimental effect of CRP on bradykinin-induced dilation was prevented.
CRP inhibits endothelium-dependent NO-mediated dilation in retinal arterioles by producing superoxide from NAD(P)H oxidase, which appears to be linked with Rho/Rho-kinase activation. By impairing endothelium-dependent NO-mediated vasoreactivity, CRP can potentially facilitate the development of retinal vascular diseases. In addition, statins are beneficial by preserving the endothelial function possibly via the inactivation of Rho/Rho-kinase pathway.
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