Institute of Normal and Pathological Physiology, Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovakia.
Department of Animal Physiology and Ethology, Faculty of Natural Sciences, Comenius University, Bratislava, Slovakia.
Oxid Med Cell Longev. 2019 Nov 22;2019:5349398. doi: 10.1155/2019/5349398. eCollection 2019.
Deficiency of nitric oxide (NO) and oxidative stress can be a cause, a consequence, or, more often, a potentiating factor for hypertension and hypertensive renal disease. Both NO and superoxide anions are radical molecules that interact with each other, leading to oxidative damage of such organs as the kidney. In the present study, we investigated the effect of chronic-specific (neuronal NOS inhibition) and nonspecific NOS inhibition on the oxidative state and antioxidant response and associated oxidative damage of the kidney of young normotensive and hypertensive rats. Young male normotensive Wistar rats (WRs, age 4 weeks) and spontaneously hypertensive rats (SHRs, age 4 weeks) were divided into three groups for each strain by the type of administered compounds. The first group was treated with 7-nitroindazole (WR+7-NI; SHR+7-NI), the second group was treated with N(G)-nitro-L-arginine-methyl ester (WR+L-NAME; SHR+L-NAME), and the control group was treated with pure drinking water (WR; SHR) continuously for up to 6 weeks. Systolic blood pressure increased in WR+L-NAME after the first week of administration and increased slightly in SHR+L-NAME in the third week of treatment. 7-NI had no effect on blood pressure. While total NOS activity was not affected by chronic NOS inhibition in any of the WR groups, it was attenuated in SHR+7-NI and SHR+L-NAME. Nitration of proteins (3-nitrotyrosine expression) was significantly reduced in WR+7NI but not in WR+L-NAME and increased in SHR+7-NI and SHR+L-NAME. Immunoblotting analysis of SOD isoforms showed decreased SOD2 and SOD3 expressions in both WR+7-NI and WR+L-NAME followed by increased SOD activity in WR+L-NAME. Conversely, increased expression of SOD2 and SOD3 was observed in SHR+L-NAME and SHR+7-NI, respectively. SOD1 expression and total activity of SOD did not change in the SHR groups. Our results show that the antioxidant defense system plays an important role in maintaining the oxidative state during NO deficiency. While the functioning antioxidant system seeks to balance the oxidation state in the renal cortex of normotensive WRs, the impaired antioxidant activity leads to the development of oxidative damage of proteins in the kidney induced by peroxynitrite in SHRs.
一氧化氮（NO）缺乏和氧化应激可能是高血压和高血压肾病的原因、后果，或者更常见的是其增强因素。NO 和超氧阴离子自由基都是相互作用的自由基分子，导致肾脏等器官的氧化损伤。在本研究中，我们研究了慢性特异性（神经元 NOS 抑制）和非特异性 NOS 抑制对年轻正常血压和高血压大鼠肾脏氧化状态、抗氧化反应及相关氧化损伤的影响。年轻雄性正常血压 Wistar 大鼠（WR，4 周龄）和自发性高血压大鼠（SHR，4 周龄）按给药类型分为每组三个亚组。第一组用 7-硝基吲唑（WR+7-NI；SHR+7-NI）处理，第二组用 N（G）-硝基-L-精氨酸甲酯（WR+L-NAME；SHR+L-NAME）处理，对照组连续饮用纯水（WR；SHR）长达 6 周。WR+L-NAME 给药后第一周内收缩压升高，SHR+L-NAME 治疗第三周内收缩压略有升高。7-NI 对血压没有影响。在任何 WR 组中，慢性 NOS 抑制均不影响总 NOS 活性，但 SHR+7-NI 和 SHR+L-NAME 中的活性减弱。WR+7-NI 中蛋白质硝化（3-硝基酪氨酸表达）显著减少，但 WR+L-NAME 中未见减少，而 SHR+7-NI 和 SHR+L-NAME 中则增加。SOD 同工酶免疫印迹分析显示，WR+7-NI 和 WR+L-NAME 中 SOD2 和 SOD3 表达减少，随后 WR+L-NAME 中 SOD 活性增加。相反，SHR+L-NAME 和 SHR+7-NI 中分别观察到 SOD2 和 SOD3 表达增加。SHR 组中 SOD1 表达和 SOD 总活性没有变化。我们的结果表明，抗氧化防御系统在 NO 缺乏时对维持氧化状态起着重要作用。在正常血压 WR 肾皮质中，功能正常的抗氧化系统试图平衡氧化状态，而在 SHR 中，受损的抗氧化活性导致由过氧亚硝酸盐诱导的肾脏蛋白质氧化损伤的发展。
