Beltowski Jerzy, Wójcicka Grazyna, Jamroz-Wiśniewska Anna, Borkowska Ewelina, Marciniak Andrzej
Department of Pathophysiology, Medical University, ul. Jaczewskiego 8, 20-090 Lublin, Poland.
Life Sci. 2005 Aug 26;77(15):1855-68. doi: 10.1016/j.lfs.2005.02.013.
Recent studies suggest that adipose tissue hormone, leptin, is involved in the pathogenesis of arterial hypertension. However, the mechanism of hypertensive effect of leptin is incompletely understood. We investigated whether antioxidant treatment could prevent leptin-induced hypertension. Hyperleptinemia was induced in male Wistar rats by administration of exogenous leptin (0.25 mg/kg twice daily s.c. for 7 days) and separate groups were simultaneously treated with superoxide scavenger, tempol, or NAD(P)H oxidase inhibitor, apocynin (2 mM in the drinking water). After 7 days, systolic blood pressure was 20.6% higher in leptin-treated than in control animals. Both tempol and apocynin prevented leptin-induced increase in blood pressure. Plasma concentration and urinary excretion of 8-isoprostanes increased in leptin-treated rats by 66.9% and 67.7%, respectively. The level of lipid peroxidation products, malonyldialdehyde + 4-hydroxyalkenals (MDA+4-HNE), was 60.3% higher in the renal cortex and 48.1% higher in the renal medulla of leptin-treated animals. Aconitase activity decreased in these regions of the kidney following leptin administration by 44.8% and 45.1%, respectively. Leptin increased nitrotyrosine concentration in plasma and renal tissue. Urinary excretion of nitric oxide metabolites (NO(x)) was 57.4% lower and cyclic GMP excretion was 32.0% lower in leptin-treated than in control group. Leptin decreased absolute and fractional sodium excretion by 44.5% and 44.7%, respectively. Co-treatment with either tempol or apocynin normalized 8-isoprostanes, MDA+4-HNE, aconitase activity, nitrotyrosine, as well as urinary excretion of NO(x), cGMP and sodium in rats receiving leptin. These results indicate that oxidative stress-induced NO deficiency is involved in the pathogenesis of leptin-induced hypertension.
近期研究表明，脂肪组织激素瘦素参与了动脉高血压的发病机制。然而，瘦素产生高血压作用的机制尚未完全明确。我们研究了抗氧化治疗是否能够预防瘦素诱导的高血压。通过皮下注射外源性瘦素（0.25mg/kg，每日两次，共7天）诱导雄性Wistar大鼠出现高瘦素血症，同时将不同组大鼠分别用超氧化物清除剂tempol或NAD(P)H氧化酶抑制剂阿扑辛（饮用水中浓度为2mM）进行处理。7天后，接受瘦素治疗的大鼠收缩压比对照组动物高20.6%。tempol和阿扑辛均能预防瘦素诱导的血压升高。接受瘦素治疗的大鼠血浆中8-异前列腺素的浓度及尿排泄量分别增加了66.9%和67.7%。在接受瘦素治疗的动物中，肾皮质脂质过氧化产物丙二醛+4-羟基烯醛（MDA+4-HNE）的水平升高了60.3%，肾髓质升高了48.1%。给予瘦素后，肾脏这些区域的乌头酸酶活性分别降低了44.8%和45.1%。瘦素使血浆和肾组织中的硝基酪氨酸浓度升高。接受瘦素治疗的大鼠尿中一氧化氮代谢产物（NO(x)）排泄量比对照组低57.4%，环磷酸鸟苷（cGMP）排泄量低32.0%。瘦素使钠的绝对排泄量和分数排泄量分别降低了44.5%和44.7%。在接受瘦素治疗的大鼠中，与tempol或阿扑辛联合治疗可使8-异前列腺素、MDA+4-HNE、乌头酸酶活性、硝基酪氨酸以及尿中NO(x)、cGMP和钠的排泄量恢复正常。这些结果表明，氧化应激诱导的一氧化氮缺乏参与了瘦素诱导的高血压发病机制。
