Obesity is associated with tissue-specific activation of renal angiotensin-converting enzyme in vivo -: Evidence for a regulatory role of endothelin
Obesity is associated with tissue-specific activation of renal angiotensin-converting enzyme in vivo -: Evidence for a regulatory role of endothelin
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DOI：
10.1161/01.hyp.35.1.329
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发表时间：
2000-01-01
期刊：
影响因子：
8.3
通讯作者：
Shaw, S
中科院分区：
文献类型：
--
作者：
Barton, M;Carmona, R;Shaw, S
在C57BL/6J小鼠模型中，我们研究了肥胖是否影响组织肾素-血管紧张素系统的功能或表达，以及内皮素(ET)-1是否参与了这些变化。在对照组(接受标准饮食)和肥胖动物30周后，单独或与口服活性ETA受体拮抗剂LU135252联合治疗，测量了肺、肾和肝脏的ACE活性(nmol.L His-Leu mg蛋白(-1))。检测肾脏血管紧张素转换酶基因的表达，并检测LU135252对纯化的人血管紧张素转换酶的影响。测定主动脉和肾组织ET-1蛋白含量，评价血管对血管紧张素II的收缩能力。肥胖与肾脏组织特异性血管紧张素转换酶活性升高(55+/-4比33+/-3nmol/L)有关，但与肺血管紧张素转换酶活性升高(34+/-2比32+/-2nmol/L)无关。长期的LU135252治疗完全阻止了这种激活(13.3+/-0.3vs55+/-4nmol/L，P
In the C57BL/6J mice model, we investigated whether obesity affects the function or expression of components of the tissue renin-angiotensin system and whether endothelin (ET)-1 contributes to these changes. ACE activity (nmol.L His-Leu.mg protein(-1)) was measured in lung, kidney, and liver in control (receiving standard chow) and obese animals treated for 30 weeks with a high-fat, low cholesterol diet alone or in combination with LU135252, an orally active ETA receptor antagonist. ACE mRNA expression was measured in the kidney, and the effects of LU135252 on purified human ACE were determined. Aortic and renal tissue ET-1 protein content was measured, and the vascular contractility to angiotensin II was assessed. Obesity was associated with a tissue-specific increase in ACE activity in the kidney (55 +/- 4 versus 33 +/- 3 nmol/L) but not in the lung (34 +/- 2 versus 32 +/- 2 nmol/L). Long-term LU135252 treatment completely prevented this activation (13.3 +/- 0.3 versus 55 +/- 4 nmol/L, P