Department of Pediatrics, Korea University Medical Center, College of Medicine, Korea University, Seoul 152-703, Korea.
Pediatr Res. 2011 May;69(5 Pt 1):378-83. doi: 10.1203/PDR.0b013e3182114c38.
Both the renin-angiotensin-aldosterone system (RAAS) and hypoxia are vital physiological factors involved in the control of nephrogenesis and vascularization. We investigated the relationship between RAAS and hypoxia in the developing kidney. The expression of VEGF and heme oxygenase (HO)-1 related with the oxygen was analyzed in the enalapril- or spironolactone-treated neonatal rat kidneys. Enalapril (30 mg/kg/d) or spironolactone (200 mg/kg/d) was administered to newborn rat pups for 7 d. The newborn rats were injected i.p. with pimonidazole (200 mg/kg), a marker of severe tissue hypoxia, 1 h before killing. VEGF and HO-1 protein expression was significantly increased by immunoblots and immunohistochemistry in both the enalapril- and spironolactone-treated kidneys, compared with the controls (p < 0.05). HO-1 mRNA expression was increased in the spironolactone-treated group (p < 0.05). The immunoactivity of pimonidazole was not different from that of the controls in the enalapril-treated group, whereas it was increased in the spironolactone-treated group. The results of this study indicate that aldosterone blockade or angiotensin II inhibition in the developing rat kidney up-regulated renal VEGF and HO-1 expression regardless of the hypoxic conditions and may differentially modulate VEGF and HO-1 production.
肾素-血管紧张素-醛固酮系统（RAAS）和缺氧都是参与肾发生和血管生成控制的重要生理因素。我们研究了发育中肾脏中 RAAS 和缺氧之间的关系。在依那普利或螺内酯处理的新生大鼠肾脏中分析了与氧气相关的 VEGF 和血红素加氧酶（HO）-1 的表达。将依那普利（30 mg/kg/d）或螺内酯（200 mg/kg/d）施用于新生大鼠幼仔，持续 7 天。在处死前 1 小时，新生大鼠腹膜内注射 pimonidazole（200 mg/kg），这是严重组织缺氧的标志物。与对照组相比，依那普利和螺内酯处理的肾脏中的 VEGF 和 HO-1 蛋白表达通过免疫印迹和免疫组织化学显着增加（p <0.05）。螺内酯处理组中 HO-1 mRNA 表达增加（p <0.05）。依那普利处理组中 pimonidazole 的免疫活性与对照组无差异，而螺内酯处理组中则增加。这项研究的结果表明，在发育中的大鼠肾脏中，醛固酮阻断或血管紧张素 II 抑制会增加肾脏 VEGF 和 HO-1 的表达，而不管缺氧情况如何，并且可能会差异调节 VEGF 和 HO-1 的产生。
