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Kidney Int. 2002 Sep;62(3):885-94.

Effect of angiotensin II antagonism on the regression of kidney disease in the rat.

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1
Mario Negri Institute for Pharmacological Research, Azienda Ospedaliera, Ospedali Riuniti di Bergamo, Via Gavazzeni 11, 24125 Bergamo, Italy. aremuzzi@marionegri.it

Abstract

BACKGROUND:

Normalization of proteinuria and even regression of glomerulosclerosis seem to occur in progressive renal disease upon blockade of the renin-angiotensin system. Here we quantified the effect of a combination of an angiotensin converting enzyme (ACE) inhibitor and an angiotensin II (Ang II) receptor antagonist on renal function and structure in spontaneous overt nephropathy in male Munich Wistar Fromter (MWF) rats.

METHODS:

Three groups of MWF rats were used: group 1 was studied at 25 weeks to provide baseline renal function and structure; group 2 was followed until 40 weeks of age; group 3 was treated with lisinopril (40 mg/L) and valsartan (180 mg/L) in drinking water from 25 to 40 weeks. A group of untreated Wistar rats (group 4, 40 weeks) was used as the control. At the end of the study renal hemodynamics, kidney tissue morphology, accumulation of type III collagen and evaluation of interstitial inflammatory cells were performed.

RESULTS:

MWF rats spontaneously developed hypertension, proteinuria, glomerulosclerosis, interstitial volume expansion and protein cast accumulation. Combined treatment completely reversed protein excretion and ameliorated renal plasma flow and the glomerular ultrafiltration coefficient. The combined therapy was effective in halting progressive glomerulosclerosis, particularly in glomeruli with mild sclerotic lesions, and reduced interstitial volume expansion. Type III collagen accumulation and protein cast also were reversed. Infiltrating cells were massively present in the interstitium already at 25 weeks, and augmented at 40 weeks in untreated rats. Combined treatment reduced infiltrating cells to values comparable to normal controls.

CONCLUSIONS:

These data indicate that in animals with spontaneous overt nephropathy, Ang II antagonism normalized proteinuria, eliminated inflammatory cell infiltration, and ameliorated glomerular and tubular structural changes.

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