Beltowski Jerzy, Wójcicka Grazyna, Marciniak Andrzej, Jamroz Anna
Department of Pathophysiology, Medical University, ul Jaczewskiego 8, 20-090 Lublin, Poland.
Life Sci. 2004 Apr 30;74(24):2987-3000. doi: 10.1016/j.lfs.2003.10.029.
Chronic hyperleptinemia induces arterial hypertension in experimental animals and may contribute to the development of hypertension in obese humans; however, the mechanism of hypertensive effect of leptin is not completely elucidated. We investigated the effect of leptin on whole-body oxidative stress, nitric oxide production, and renal sodium handling. The study was performed on male Wistar rats divided into 3 groups: 1) control, fed standard chow ad libitum, 2) leptin-treated group, receiving leptin injections (0.25 mg/kg twice daily s.c. for 7 days), 3) pair-fed group, in which food intake was adjusted to the leptin group. Leptin caused 30.5% increase in systolic blood pressure. Plasma concentration and urinary excretion of 8-isoprostanes in animals receiving leptin was 46.4% and 49.2% higher, respectively. The level of lipid peroxidation products, malonyldialdehyde + 4-hydroxyalkenals, increased by 52.5% in the renal cortex and by 48.4% in the renal medulla following leptin treatment, whereas aconitase activity decreased in these regions of the kidney by 45.3% and 39.2%, respectively. Urinary excretion of nitric oxide metabolites (NOx) was 55.0% lower, and fractional excretion of NOx was 55.8% lower in the leptin-treated group. Urinary excretion of cGMP decreased in leptin-treated rats by 26.3%. Following leptin treatment, absolute and fractional sodium excretion decreased by 35.0% and 41.2%, respectively. These results indicate that hyperleptinemia induces systemic and intrarenal oxidative stress, decreases the amount of bioactive NO possibly due to its degradation by reactive oxygen species, and causes renal sodium retention by stimulating tubular sodium reabsorption. NO deficiency and abnormal renal Na+ handling may contribute to leptin-induced hypertension.
慢性高瘦素血症可在实验动物中诱发动脉高血压，并可能促使肥胖人群发生高血压；然而，瘦素的高血压作用机制尚未完全阐明。我们研究了瘦素对全身氧化应激、一氧化氮生成及肾脏钠处理的影响。本研究以雄性Wistar大鼠为对象，分为3组：1）对照组，自由摄食标准饲料；2）瘦素治疗组，接受瘦素注射（0.25 mg/kg，皮下注射，每日2次，共7天）；3）配对喂养组，食物摄入量调整至与瘦素组相同。瘦素使收缩压升高30.5%。接受瘦素的动物血浆中8-异前列腺素的浓度及尿排泄量分别升高46.4%和49.2%。瘦素治疗后，肾皮质和肾髓质中脂质过氧化产物丙二醛+4-羟基烯醛的水平分别升高52.5%和48.4%，而这些肾脏区域的乌头酸酶活性分别降低45.3%和39.2%。瘦素治疗组中一氧化氮代谢产物（NOx）的尿排泄量降低55.0%，NOx的排泄分数降低55.8%。瘦素治疗的大鼠中cGMP的尿排泄量降低26.3%。瘦素治疗后，钠的绝对排泄量和排泄分数分别降低35.0%和41.2%。这些结果表明，高瘦素血症可诱发全身和肾脏内的氧化应激，可能由于活性氧对生物活性一氧化氮（NO）的降解作用而使其生成量减少，并通过刺激肾小管钠重吸收导致肾脏钠潴留。NO缺乏和肾脏钠处理异常可能促成了瘦素诱发的高血压。
