Rodriguez-Iturbe Bernardo, Sepassi Lili, Quiroz Yasmir, Ni Zhenmin, Wallace Douglas C, Vaziri Nosratola D
Renal Service and Laboratory, Instituto de Investigaciones Biomédicas (Fundacite-Zulia), Hospital Universitario, Universidad del Zulia, Maracaibo, Venezuela.
J Appl Physiol (1985). 2007 Jan;102(1):255-60. doi: 10.1152/japplphysiol.00513.2006. Epub 2006 Oct 5.
Mitochondria are the major source of superoxide (O(2)(-)) in the aerobic organisms. O(2)(-) produced by the mitochondria is converted to hydrogen peroxide by mitochondrial superoxide dismutase (SOD2). Mice with complete SOD2 deficiency (SOD2(-/-)) exhibit dilated cardiomyopathy and fatty liver leading to neonatal mortality, whereas mice with partial SOD2 deficiency (SOD2(+/-)) show evidence of O(2)(-)-induced mitochondrial damage resembling cell senescence. Since earlier studies have provided compelling evidence for the role of oxidative stress and tubulointerstitial inflammation in the pathogenesis of hypertension, we tested the hypothesis that partial SOD2 deficiency may result in hypertension. Wild-type (SOD2(+/+)) and partial SOD2-deficient (SOD2(+/-)) mice had similar blood pressures at 6-7 mo of age, but at 2 yr SOD2(+/-) mice had higher blood pressure. Oxidative stress, renal interstitial T-cell and macrophage infiltration, tubular damage, and glomerular sclerosis were all significantly increased in 2-yr-old SOD2(+/-) mice. High-salt diet induced hypertension in 6-mo-old SOD2-deficient mice but not in wild-type mice. In conclusion, partial SOD2 deficiency results in oxidative stress and renal interstitial inflammation, changes compatible with accelerated renal senescence and salt-sensitive hypertension. These findings are consistent with the pattern described in numerous other models of salt-sensitive hypertension and resemble that commonly seen in elderly humans.
线粒体是需氧生物中超氧化物（O₂⁻）的主要来源。线粒体产生的O₂⁻通过线粒体超氧化物歧化酶（SOD2）转化为过氧化氢。完全缺乏SOD2的小鼠（SOD2⁻/⁻）表现出扩张型心肌病和脂肪肝，导致新生儿死亡，而部分缺乏SOD2的小鼠（SOD2⁺/⁻）则显示出O₂⁻诱导的类似于细胞衰老的线粒体损伤证据。由于早期研究已经为氧化应激和肾小管间质炎症在高血压发病机制中的作用提供了令人信服的证据，我们测试了部分SOD2缺乏可能导致高血压的假说。野生型（SOD2⁺/⁺）和部分SOD2缺陷型（SOD2⁺/⁻）小鼠在6-7月龄时血压相似，但在2岁时SOD2⁺/⁻小鼠血压更高。2岁的SOD2⁺/⁻小鼠的氧化应激、肾间质T细胞和巨噬细胞浸润、肾小管损伤和肾小球硬化均显著增加。高盐饮食在6月龄的SOD2缺陷型小鼠中诱发高血压，但在野生型小鼠中未诱发。总之，部分SOD2缺乏导致氧化应激和肾间质炎症，这些变化与加速的肾衰老和盐敏感性高血压相一致。这些发现与许多其他盐敏感性高血压模型中描述的模式一致，并且类似于在老年人中常见的模式。
