Purchase this article with an account.
Taiji Nagaoka, Tsuneaki Omae, Ichiro Tanano, Akitoshi Yoshida; Homocysteine Inhibits Endothelial-dependent Nitric Oxide-mediated Dilation Of Retinal Arterioles Via Enhanced Superoxide Production. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6841.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Homocysteine, a sulfur-containing amino acid, is an emerging risk factor for cardiovascular diseases. Furthermore, recent epidemiological studies confirm that elevated homocysteine levels are associated with ocular vascular diseases. However, the direct effect of homocysteine on ocular microvascular reactivity remains unknown. Herein, we examined whether homocysteine can affect endothelium-dependent nitric oxide (NO)-mediated dilation of retinal arterioles and whether oxidative stress and distinct protein kinase signaling pathways are involved in the homocysteine-mediated effect.
Porcine retinal arterioles were isolated, cannulated, and pressurized without flow in vitro. Diameter changes were recorded using videomicroscopic techniques.
Intraluminal treatment with homocysteine (1 mM, 180 minutes) significantly attenuated arteriolar dilation to endothelium-dependent NO-mediated agonists bradykinin and A23187 but not to endothelium- independent NO donor sodium nitroprusside. In the presence of superoxide scavenger TEMPOL, NAD(P)H oxidase inhibitor apocynin, p38 kinase inhibitor SB203580, or pioglitazone, but not xanthine oxidase inhibitor allopurinol, JNK inhibitor SP600125 and pioglitazone with GW9662, peroxisome proliferator-activated receptor-γ inhibitor (PPAR-γ), the detrimental effect of homocysteine on bradykinin-induced dilation was prevented.
Homocysteine inhibits endothelium-dependent NO-mediated dilation in retinal arterioles by producing superoxide from NAD(P)H oxidase, which appears to be linked with p38 kinase. By impairing endothelium- dependent NO-mediated vasoreactivity, homocysteine can potentially facilitate the development of retinal vascular diseases. In addition, pioglitazone are beneficial by preserving endothelial function, possibly through activation of PPAR-γ.
This PDF is available to Subscribers Only