Effect of enalapril and losartan on the events that precede diabetic nephropathy in rats.

Mesangial cell proliferation, phenotype change, and increased transforming growth factor-beta (TGF-beta) precede mesangial expansion in diabetic rats. Experiments using mesangial cell culture have shown that angiotensin II increases TGF-beta production by these cells. The aim of the present study was to investigate the effect of enalapril and losartan on the events that precede diabetic nephropathy in rats. It was also analyzed if the determination of urinary TGF-beta could be a mean for the evaluation of therapeutic efficacy in this disease. Eighty-two female Wistar rats were made diabetic by intravenous injection of streptozotocin diluted in citrate buffer, and citrate buffer alone was injected into the control group (N = 34). Ten days later, the right kidney was removed. Thirty diabetic rats were treated with enalapril, DMN + E, in drinking water (20 mg/L) and 24 with losartan, DMN + L (50 mg/L). Urinary TGF-beta was determined 90 days after STZ or buffer injection, the animals were killed, and the kidneys were removed for histological and immunohistochemical studies. The immunostaining for TGF-beta and fibronectin in the cortical tubulointerstitium and glomeruli was higher in untreated diabetic rats (p < 0.001). Treatment with enalapril or losartan reduced this increase. The urinary TGF-beta excretion (pg/mg urinary creatinine) was 48.6 +/- 5.9 in control animals, 603.9 +/- 80.41 in untreated diabetic rats, 279.3 +/- 47.0 in diabetic rats treated with enalapril, and 243.7 +/- 40.0 in rats treated with losartan. We concluded that enalapril or losartan treatment can modify events that precede diabetic nephropathy by reducing TGF-beta and fibronectin expression in glomeruli and tubulointerstitium as well as urinary TGF-beta content.

Volpini RA ，da Silva CG ，Costa RS ，Coimbra TM ... -  《DIABETES-METABOLISM RESEARCH AND REVIEWS》

Renin-angiotensin system blockade prevents the increase in plasma transforming growth factor beta 1, and reduces proteinuria and kidney hypertrophy in the streptozotocin-diabetic rat.

Erman A ，Veksler S ，Gafter U ，Boner G ，Wittenberg C ，van Dijk DJ ... -  《JOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM》

Increased renal GLUT1 abundance and urinary TGF-beta 1 in streptozotocin-induced diabetic rats: implications for the development of nephropathy complicating diabetes.

D'Agord Schaan B ，Lacchini S ，Bertoluci MC ，Irigoyen MC ，Machado UF ，Schmid H ... -  《HORMONE AND METABOLIC RESEARCH》

Renoprotective effects of valsartan and enalapril in STZ-induced diabetes in rats.

Kalender B ，Oztürk M ，Tunçdemir M ，Uysal O ，Dagistanli FK ，Yegenaga I ，Erek E ... -  《ACTA HISTOCHEMICA》

Impact of renal denervation on renal content of GLUT1, albuminuria and urinary TGF-beta1 in streptozotocin-induced diabetic rats.

D'Agord Schaan B ，Lacchini S ，Bertoluci MC ，Irigoyen MC ，Machado UF ，Schmid H ... -  《AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL》