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首页> 外文期刊>Journal of Cellular Physiology >Para-Cresyl Sulfate Acutely Impairs Vascular Reactivity and Induces Vascular Remodeling
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Para-Cresyl Sulfate Acutely Impairs Vascular Reactivity and Induces Vascular Remodeling

机译：Para-Cresyl硫酸严重损害血管反应和诱导血管重建

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Chronic kidney disease (CKD) is characterized by vascular remodeling and the retention of uremic toxins, several of which are independently associated with the high cardiovascular mortality rate in CKD patients. Whether the association between these uremic toxins and cardiovascular mortality is due to induction of vascular dysfunction and resulting vascular remodeling remains to be determined. This study evaluates the effects of para-cresyl sulfate (PCS), a newly identified uremic toxin, on vascular function and remodeling. PCS acutely induced oxidative stress in both endothelial and vascular smooth muscle cells, with a maximal effect at 0.15 mM, corresponding to the mean "uremic" concentration found in dialysis patients. PCS significantly increased within 30 min phenylephrine-induced contraction of mouse thoracic aorta, through direct activation of rho-kinase, independently of oxidative stress induction, as demonstrated by the capacity of rho-kinase inhibitor Y-27632 to abolish this effect. After exposure of the aorta to PCS for 48 h, we observed inward eutrophic remodeling, a hallmark of uremic vasculopathy characterized by a reduction of the area of both lumen and media, with unchanged media/lumen ratio. In conclusion, elevated PCS concentrations such as those observed in CKD patients, by promoting both vascular dysfunction and vascular remodeling, may contribute to the development of hypertension and to cardiovascular mortality in CKD. (C) 2015 Wiley Periodicals, Inc.
机译：慢性肾脏疾病(CKD)的特点是尿毒症的血管重建和保留毒素,几个独立的与高心血管死亡率有关在CKD患者。这些尿毒症毒素和心血管疾病之间的关系死亡率是由于血管的感应功能障碍和血管重建还有待确定。para-cresyl硫酸盐(pc)的影响,新发现尿毒症毒素,对血管功能重构。内皮细胞和血管平滑肌细胞,在0.15毫米,最大效应的意思是“尿毒症”对应的浓度在透析病人。在30分钟phenylephrine-induced增加大鼠胸主动脉收缩,通过直接激活rho-kinase,独立的氧化应激诱导,如证明了rho-kinase抑制剂y - 27632的能力废除这一效应。为48小时电脑,我们观察到内在的富营养的装修,尿毒症的血管病变的一个特点以减少的面积媒体/腔腔和媒体,不变比率。比如CKD患者中观察到促进血管功能障碍和血管装修,可能导致的发展高血压和心血管死亡率慢性肾病。

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