Ruíz-Ortega M, Gómez-Garre D, Alcázar R, Palacios I, Bustos C, González S, Plaza J J, González E, Egido J
Jiménez Díaz Foundation, Autónoma University, Madrid, Spain.
J Hypertens Suppl. 1994 Jul;12(4):S51-8.
To review the evidence that links angiotensin II and endothelin as growth factors and as modifiers of extracellular matrix synthesis in renal cells, with particular reference to the effects of angiotensin converting enzyme (ACE) inhibition in models of renal injury.
In cultured mesangial cells, both angiotensin II and endothelin promote contraction, proliferation/hypertrophy, signal transduction pathways, the activation of early growth genes, and the generation of inflammatory mediators, cytokines and growth factors. Both hormones have been shown to promote the synthesis of fibronectin and collagen in a dose-dependent manner. ACE inhibition attenuates the effect of endothelin-1, one of three isoforms of endothelin.
In experimental models of renal injury, chiefly in those characterized by increased intraglomerular pressure, ACE inhibition has reduced proteinuria and glomerular and interstitial sclerosis.
ACE inhibition has been shown to have major beneficial effects in patients with diabetic nephropathy, even in those with normal blood pressure.
Although the renal-protective effects of ACE inhibitors in experimental and human renal injury may reflect systemic and/or local hemodynamic effects of these drugs, their modulatory actions on extracellular matrix synthesis and proteinuria may contribute to the benefit of ACE-inhibitor therapy.
回顾将血管紧张素II和内皮素作为生长因子以及肾细胞外基质合成调节因子的相关证据，尤其参考血管紧张素转换酶（ACE）抑制在肾损伤模型中的作用。
在培养的系膜细胞中，血管紧张素II和内皮素均能促进收缩、增殖/肥大、信号转导通路、早期生长基因的激活以及炎症介质、细胞因子和生长因子的产生。两种激素均已被证明能以剂量依赖的方式促进纤连蛋白和胶原蛋白的合成。ACE抑制可减弱内皮素-1（内皮素三种异构体之一）的作用。
在肾损伤的实验模型中，主要是那些以肾小球内压升高为特征的模型，ACE抑制可减少蛋白尿以及肾小球和间质硬化。
已证明ACE抑制对糖尿病肾病患者有主要的有益作用，即使是血压正常的患者。
尽管ACE抑制剂在实验性和人类肾损伤中的肾保护作用可能反映了这些药物的全身和/或局部血流动力学效应，但其对细胞外基质合成和蛋白尿的调节作用可能有助于ACE抑制剂治疗的益处。
