Effects of angiotensin inhibitors on renal injury and angiotensin receptor expression in early hypertensive nephrosclerosis.
Effects of angiotensin inhibitors on renal injury and angiotensin receptor expression in early hypertensive nephrosclerosis.
复制标题
血管紧张素抑制剂对早期高血压肾硬化肾损伤和血管紧张素受体表达的影响。
作者：
H. Nakaya;H. Sasamura;Y. Kitamura;T. Amemiya;K. Konishi;M. Hayashi;T. Saruta
已知血管紧张素转换酶抑制剂(ACEI)可抑制已建立的肾功能衰竭的进展。这项研究的目的是比较血管紧张素转换酶抑制剂和AT1受体拮抗剂(AT1R-Ant)在高血压肾硬化早期预防肾脏疾病发展的效果。SHRSP/IZM大鼠(n=61)给予ACEI地拉普利(40 mg/kg/d)或AT1R-Ant坎地沙坦酯(1 mg/kg/d)治疗10wk~22wk。在第14周和第22周评估尿蛋白和结构/超微结构的变化。任何一种药物的治疗都能降低血压和心血管肥厚。14wk时既无蛋白尿，也无主要肾脏组织学改变。然而，在22周时，未经治疗的SHRSP/IZM患者出现蛋白尿并伴有肾硬化性改变。用ACEI或AT1R-Ant治疗后，蛋白尿的减少相似(未治疗，32.2+/-7.4；地拉普利治疗，5.5+/-1.2；坎地沙坦治疗，3.9+/-0.3 mg/100g/d)。在22wk时，SHRSP/IZM组出现明显的中小型肾动脉硬化，但ACEI和AT1R-Ant组的硬化程度与未治疗组相似。两组大鼠肾小球超微结构无明显差异。在整个研究过程中，肾脏AT1a或AT1b受体亚型的mRNA表达没有明显变化。相反，药物治疗组在14wk时AT2受体基因表达下降，但在22wk时未见下降。这些结果表明，ACEI和AT1R-Ant在减轻早期高血压性肾硬化症的肾损伤方面具有相似的疗效，两者的治疗都与AT2受体mRNA表达的一过性下降有关。
Angiotensin converting enzyme inhibitors (ACEI) are known to inhibit the progression of established renal failure. The aim of this study was to compare the efficacy of an ACEI and an AT1 receptor antagonist (AT1R-Ant) in preventing the development of renal disease, at an early stage of hypertensive nephrosclerosis. SHRSP/Izm rats (n = 61) were treated from 10 wk until 22 wk with the ACEI delapril (40 mg/kg/d) or the AT1R-Ant candesartan cilexetil (1 mg/kg/d). Proteinuria, and structural/ultrastructural changes were assessed at 14 and 22 wk. Treatment with either agent resulted in reductions in blood pressure and cardiovascular hypertrophy. Neither proteinuria nor major renal histological changes were evident at 14 wk. At 22 wk, however, proteinuria accompanied by nephrosclerotic changes was seen in the untreated SHRSP/Izm. Treatment with either ACEI or AT1R-Ant resulted in similar reductions in proteinuria (untreated, 32.2 +/- 7.4; delapril-treated, 5.5 +/- 1.2; candesartan-treated, 3.9 +/- 0.3 mg/100 g/d). Prominent sclerosis of small-to-medium sized renal arteries was seen in the untreated SHRSP/Izm at 22 wk, but was similarly attenuated by the ACEI and AT1R-Ant. The glomerular ultrastructure was comparable between the two groups. No significant changes in renal AT1a or AT1b receptor subtype mRNA expression were seen throughout the course of the study. In contrast, a decrease in AT2 receptor mRNA was seen in the drug-treated groups at 14 wk but not at 22 wk. These results suggest that both ACEI and AT1R-Ant have similar efficacy in attenuating the onset of renal injury in early hypertensive nephrosclerosis, and that treatment with either agent is associated with a transient decrease in AT2 receptor mRNA expression.
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影响因子：
15.9
作者：
LAFAYETTE, RA;MAYER, G;MEYER, TW
通讯作者：
MEYER, TW
DOI：
10.1152/ajprenal.1998.274.3.f623
发表时间：
1998-03
期刊：
American journal of physiology. Renal physiology
影响因子：
--
作者：
Mukut Sharma;Ramratan Sharma;A. Greene;E. McCarthy;V. Savin
通讯作者：
Mukut Sharma;Ramratan Sharma;A. Greene;E. McCarthy;V. Savin
影响因子：
3.6
作者：
B. Lassègue;R. Alexander;G. Nickenig;M. Clark;T. Murphy;K. Griendling
通讯作者：
B. Lassègue;R. Alexander;G. Nickenig;M. Clark;T. Murphy;K. Griendling
DOI：
10.1172/jci119531
发表时间：
1997-07
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
H. Siragy;Robert M. Carey
通讯作者：
H. Siragy;Robert M. Carey
血管紧张素合成途径和受体亚型的异质性：生理学和药理学意义。
DOI：
--
发表时间：
1993
期刊：
Journal of hypertension. Supplement : official journal of the International Society of Hypertension
影响因子：
--
作者：
Dzau,VJ;Sasamura,H;Hein,L
通讯作者：
Hein,L