Nitrative stress participates in aging-related vascular endothelial dysfunction

doi:10.3969/j.issn.1006-7795.2015.06.013

Abstract

Abstract: Objective This study aimed to observe the effect of nitrative stress on the morphology and function of vascular endothelium in the natural aging rats. Methods Young(3 months) and aging(20 months) male SD rats(SPF grade) were randomly divided into four groups, with ten rats in each group: 1 3 months control;2 3 months+Fe(III) meso-tetra(N-methyl-4-pyridyl) porphine pentachloride(FeTMPyP);3 20 months control;4 20 months+FeTMPyP. The experimental groups were given FeTMPyP(peroxynitrite scavenger;3 mg/kg every 3 days;totally 5 times) via intraperitoneal injection. The levels of aging-related proteins P53 and P21 in liver were detected by Western blotting. Rat thoracic aortas was isolated and connected to an isometric force transducer. Endothelium-dependent dilation was measured by classic drugs, such as different concentrations of acetylcholine(ACh). The histological changes of thoracic aortas were observed by HE staining. The 3-nitrotyrosine and endothelium markers vWF and endothelial nitric oxide synthase(eNOS) levels in vascular tissues were detected by immunohistochemistry. Results In 20 months old rats, the endothelium-dependent relaxation in aortas was dropped significantly than the 3 months rats. Adoption of peroxynitrite scavenger FeTMPyP intervention can obviously improve the endothelium-dependent relaxation of aging rats. Both HE and von willebrand factor(vWF) & eNOS immunohistochemistry staining results showed that there were obvious morphological damage in thoracic aorta in 20 months old rats. Adoption of peroxynitrite scavenger FeTMPyP intervention can obviously reduce the damage of aging vascular morphology. Immunohistochemistry results showed that in aged thoracic aortas, the 3-nitrotyrosine levels increased significantly, which indicated the obvious nitrative stress reaction. Adoption of peroxynitrite scavenger FeTMPyP intervention can obviously reduce the 3-nitrotyrosine levels. Conclusion During aging, the increased formation of peroxynitrite and enhanced nitrative stress reaction can lead to endothelial injury and functional decline.

Key words: aging, nitrative stress, vascular endothelium

CLC Number:

R363

Ma Yuman, Sun Qi, Dong Yu, Wang Huanyuan, Wang Wen. Nitrative stress participates in aging-related vascular endothelial dysfunction[J]. Journal of Capital Medical University, 2015, 36(6): 908-914.

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URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2015.06.013

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2015/V36/I6/908

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