Control of glomerular hyperfiltration and renal hypertrophy by an angiotensin converting enzyme inhibitor prevents the progression of renal damage in hypertensive diabetic rats
Control of glomerular hyperfiltration and renal hypertrophy by an angiotensin converting enzyme inhibitor prevents the progression of renal damage in hypertensive diabetic rats
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DOI：
10.1097/00004872-199917121-00023
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发表时间：
1999-12-01
影响因子：
4.9
通讯作者：
Carretta, R
中科院分区：
文献类型：
--
作者：
Fabris, B;Candido, R;Carretta, R
目的肾小球高滤过和肾脏肥大在糖尿病肾病的发生发展中起重要作用。本研究的目的是比较等效的降低血压所产生的血管紧张素转换酶（ACE）抑制剂螺环内酯（SPI）和肼苯哒嗪，利血平和氢氯噻嗪（HRH）的抗高血压三联药物组合对肾功能，蛋白尿和肾脏结构的影响高血压糖尿病rates.Design和方法四组动物进行了评估，在短期和长期的研究。在两项研究中，一组作为非糖尿病高血压对照（H）。其他三组均为糖尿病患者，并被分配到以下组之一：第一组糖尿病患者未接受特定治疗（HD），第二组糖尿病患者接受SPI治疗（HD-SPI），第三组糖尿病患者接受HRH治疗（HD-HRH）。结果SPI组和HRH组大鼠血压下降幅度相同，HD组肾小球滤过率（GFR）、尿蛋白、肾小球面积、近端肾小管面积、肾小球硬化率均显著增加，无论是短期还是长期的研究。在HD-SPI组中，糖尿病高滤过和肾脏肥大反应被阻止。在HD-HRH组中，GFR和蛋白尿在糖尿病后期略有减少，而肾小球面积和肾小管面积不受影响。肾脏病变的半定量分析表明，SPI是更有效的比HRH在预防肾小球硬化症的发展。结论本研究的结果表明，SPI的早期适应性超滤和肾脏肥大的控制可能是相关的肾小球硬化症的预防。(C)利平科特威廉姆斯&威尔金斯。
Objective Glomerular hyperfiltration and renal hypertrophy are both considered important in the progression of diabetic nephropathy. The aim of this study was to compare the effects of an equivalent reduction in blood pressure produced by the angiotensin-converting enzyme (ACE) inhibitor spirapril (SPI) and an antihypertensive triple drug combination of hydralazine, reserpine and hydrochlorothiazide (HRH) on kidney function, proteinuria and renal structure in hypertensive diabetic rats.Design and methods Four groups of animals were evaluated in short-term and long-term studies. In both studies one group served as a non-diabetic hypertensive control (H). The other three groups were rendered diabetic and were allocated to one of the following groups: the first diabetic group received no specific therapy (HD), the second diabetic group was treated with SPI (HD-SPI) and the third diabetic group was treated with HRH (HD-HRH). In each of the two studies the systolic blood pressure (SBP), 24 h urinary total protein, glomerular filtration rate (GFR), glomerular area, proximal tubular area and glomerular sclerosis were evaluated.Results The blood pressure reduction was equal in rats receiving either SPI or HRH, The GFR, proteinuria, glomerular area and tubular area were significantly increased in the HD group, both in the short-term and the long-term study. In the HD-SPI group the diabetic hyperfiltration and renal hypertrophy responses were prevented. In the HD-HRH group the GFR and proteinuria were slightly reduced in the later phases of diabetes, while the glomerular area and tubular area were not affected. Semiquantitative analysis of renal lesions showed that SPI was more effective than HRH in the prevention of the development of glomerulosclerosis.Conclusions The results of this study suggest that the control of early adaptive hyperfiltration and renal hypertrophy by SPI may be relevant in the prevention of glomerulosclerosis. (C) Lippincott Williams & Wilkins.