Tojo Akihiro, Onozato Maristela Lika, Kobayashi Naohiko, Goto Atsuo, Matsuoka Hiroaki, Fujita Toshiro
Division of Nephrology and Endocrinology, Department of Internal Medicine, University of Tokyo, Tokyo, Japan.
Hypertension. 2002 Dec;40(6):834-9. doi: 10.1161/01.hyp.0000039506.43589.d5.
Reactive oxygen species have an important pathogenic role in organ damage. We investigated the role of oxidative stress via nicotinamide adenine dinucleotide phosphate (NAD[P]H) oxidase in the kidney of the Dahl salt-sensitive (DS) rats with heart failure (DSHF). Eleven-week-old DS rats fed an 8%-NaCl diet received either vehicle or imidapril (1 mg/kg per day) for 7 weeks. The renal expression of the NAD(P)H oxidase p47phox and endothelial NO synthase were evaluated. In DSHF rats, associated with increased renal angiotensin II, mRNA and protein expression of NAD(P)H oxidase p47phox were enhanced with an increase in renal lipid peroxidation production (0.33+/-0.03 versus 0.22+/-0.01 nmol/mg protein, P<0.05) and urinary excretion of hydrogen peroxide (26.9+/-6.6 versus 9.5+/-2.1 U/mg creatinine, P<0.01) compared with levels in Dahl salt-resistant rats. The endothelial NO synthase expression was decreased in the kidney. Treatment with imidapril reduced renal angiotensin II and NAD(P)H oxidase expression and the oxidative products (kidney lipid peroxidation product: 0.16+/-0.02, P<0.001; urinary hydrogen peroxide: 3.1+/-0.2, P<0.01 versus DSHF rats). Imidapril significantly decreased albuminuria and reduced glomerulosclerosis without changes in the blood pressure. In conclusion, DSHF rats showed increased oxidative stress in the kidney via NAD(P)H oxidase. Blockade of local angiotensin II with subpressor dose of imidapril inhibited NAD(P)H oxidase and prevented renal damage.
活性氧在器官损伤中具有重要的致病作用。我们研究了通过烟酰胺腺嘌呤二核苷酸磷酸（NAD[P]H）氧化酶产生的氧化应激在心力衰竭的 Dahl 盐敏感（DS）大鼠肾脏中的作用。给 11 周龄喂食 8%氯化钠饮食的 DS 大鼠每日给予溶剂或依那普利（1 mg/kg），持续 7 周。评估肾脏中 NAD(P)H 氧化酶 p47phox 和内皮型一氧化氮合酶的表达。在 DSHF 大鼠中，与肾脏血管紧张素 II 增加相关，NAD(P)H 氧化酶 p47phox 的 mRNA 和蛋白表达增强，同时肾脏脂质过氧化产物增加（0.33±0.03 对 0.22±0.01 nmol/mg 蛋白，P<0.05），过氧化氢尿排泄增加（26.9±6.6 对 9.5±2.1 U/mg 肌酐，P<0.01），与 Dahl 盐抵抗大鼠相比。肾脏中的内皮型一氧化氮合酶表达降低。依那普利治疗可降低肾脏血管紧张素 II 和 NAD(P)H 氧化酶表达以及氧化产物（肾脏脂质过氧化产物：0.16±0.02，P<0.001；尿过氧化氢：3.1±0.2，与 DSHF 大鼠相比 P<0.01）。依那普利显著降低蛋白尿并减轻肾小球硬化，而血压无变化。总之，DSHF 大鼠通过 NAD(P)H 氧化酶在肾脏中表现出氧化应激增加。用亚降压剂量的依那普利阻断局部血管紧张素 II 可抑制 NAD(P)H 氧化酶并预防肾脏损伤。
