Enalapril and losartan attenuate mitochondrial dysfunction in aged rats
Enalapril and losartan attenuate mitochondrial dysfunction in aged rats
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DOI：
10.1096/fj.02-0063fje
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发表时间：
2003-04-01
期刊：
影响因子：
4.8
通讯作者：
Fraga, CG
中科院分区：
文献类型：
--
作者：
de Cavanagh, EMV;Piotrkowski, B;Fraga, CG
肾素-血管紧张素系统（RAS）抑制剂可以减弱衰老对肾功能和结构的影响，但其对线粒体衰老的影响尚不清楚。为了研究血管紧张素转换酶抑制剂（依那普利）或血管紧张素II受体阻滞剂（氯沙坦）是否可以减轻肾脏线粒体中与年龄相关的变化，雄性Wistar大鼠（14月龄）在8个月期间接受含有依那普利（10 mg/kg/天）（Enal）或氯沙坦（30 mg/kg/天）（Los）或不添加（Old）的水。还研究了4个月大的未处理大鼠（年轻）。在老年大鼠线粒体呼吸控制，ADP/O，一氧化氮合酶活性，和解偶联蛋白2水平较低（46，42，27，和76%，分别），Mn-SOD活性较高（70%）比年轻，Enal，和洛杉矶大鼠。老年大鼠线粒体过氧化氢的产生高于年轻（197%）和Enal或Los（40%）大鼠。在老年大鼠中，肾脏GSH/GSSG低于年轻（80%）和Enal（57%）或Los（68%）大鼠。在老年大鼠的电子显微镜显示，在肾小管上皮细胞的微绒毛消失，不明确的线粒体嵴，线粒体数量减少，和增加的嗜锇小体的数量相对年轻，Enal，或洛杉矶大鼠。总之，依那普利和氯沙坦可以防止年龄相关的线粒体功能障碍和超微结构的改变，强调RAS在衰老过程中的作用。建议与氧化应激调节的关联。
Renin-angiotensin system (RAS) inhibition can attenuate the effects of aging on renal function and structure; however, its effect on mitochondrial aging is unknown. To investigate whether an angiotensin-converting enzyme inhibitor (enalapril) or an angiotensin II receptor blocker (losartan) could mitigate age-associated changes in kidney mitochondria, male Wistar rats (14 mo old) received during 8 mo water containing either enalapril (10 mg/kg/day) (Enal), or losartan (30 mg/kg/day) (Los), or no additions (Old). Four-month-old untreated rats (Young) were also studied. In Old rats mitochondrial respiratory control, ADP/O, nitric oxide synthase activity, and uncoupling protein 2 levels were lower (46, 42, 27, and 76%, respectively), and Mn-SOD activity was higher (70%) than in Young, Enal, and Los rats. In Old rats mitochondrial hydrogen peroxide production was higher than in both Young (197%) and Enal or Los (40%) rats. In Old rats, kidney GSH/GSSG was lower than in both Young (80%) and Enal (57%) or Los (68%) rats. In Old rats electron microscopy showed effacement of microvilli in tubular epithelial cells, ill-defined mitochondrial cristae, lower mitochondrial numbers, and enhanced number of osmiophilic bodies relative to Young, Enal, or Los rats. In conclusion, enalapril and losartan can protect against both age-related mitochondrial dysfunction and ultrastructural alterations, underscoring the role of RAS in the aging process. An association with oxidative stress modulation is suggested.