Greene E L, Kren S, Hostetter T H
Department of Medicine, Renal Division, University of Minnesota, Minneapolis 55455, USA.
J Clin Invest. 1996 Aug 15;98(4):1063-8. doi: 10.1172/JCI118867.
The renin-angiotensin-aldosterone system (RAAS) participates in the injury sustained by the remnant kidney. Our studies assessed the importance of aldosterone in that model and the response of aldosterone to drugs interfering with the RAAS. Initially, four groups of rats were studied: SHAM-operated rats, untreated remnant rats (REM), REM rats treated with losartan and enalapril (REM AIIA), and REM AIIA rats infused with exogenous aldosterone (REM AIIA + ALDO). The last group was maintained with aldosterone levels comparable to those in untreated REM rats by constant infusion of exogenous aldosterone. REM rats had larger adrenal glands and a > 10-fold elevation in plasma aldosterone compared to SHAM. REM AIIA rats demonstrated significant suppression of the hyperaldosteronism as well as marked attenuation of proteinuria, hypertension, and glomerulosclerosis compared to REM. REM AIIA + ALDO rats manifested greater proteinuria, hypertension, and glomerulosclerosis than REM AIIA rats. Indeed, by 4 wk of observation all of these features of the experimental disease were similar in magnitude in REM AIIA + ALDO and untreated REM. In separate REM rats spironolactone administration did not reduce glomerular sclerosis but did transiently reduce proteinuria, lowered arterial pressure, and lessened cardiac hypertrophy. In summary, aldosterone contributes to hypertension and renal injury in the remnant kidney model.
肾素-血管紧张素-醛固酮系统(RAAS)参与残余肾所受的损伤。我们的研究评估了醛固酮在该模型中的重要性以及醛固酮对干扰RAAS的药物的反应。最初,研究了四组大鼠:假手术大鼠、未治疗的残余肾大鼠(REM)、用氯沙坦和依那普利治疗的REM大鼠(REM AIIA)以及输注外源性醛固酮的REM AIIA大鼠(REM AIIA + ALDO)。通过持续输注外源性醛固酮,使最后一组大鼠的醛固酮水平维持在与未治疗的REM大鼠相当的水平。与假手术大鼠相比,REM大鼠的肾上腺更大,血浆醛固酮升高10倍以上。与REM大鼠相比,REM AIIA大鼠的醛固酮增多症得到显著抑制,蛋白尿、高血压和肾小球硬化也明显减轻。与REM AIIA大鼠相比,REM AIIA + ALDO大鼠表现出更严重的蛋白尿、高血压和肾小球硬化。事实上,经过4周的观察,实验性疾病的所有这些特征在REM AIIA + ALDO大鼠和未治疗的REM大鼠中程度相似。在另一组REM大鼠中,给予螺内酯并未减轻肾小球硬化,但确实能短暂减少蛋白尿、降低动脉血压并减轻心脏肥大。总之,醛固酮在残余肾模型中导致高血压和肾损伤。