Effects of amlodipine on tubulointerstitial lesions in normotensive hyperoxaluric rats.

Abstract

Although controversial, a number of reports have suggested that calcium antagonists can retard or prevent the progression of various renal diseases in experimental models. Nevertheless, there are few data related to tubulointerstitial changes in these studies. On the other hand, hyperoxaluria is a recognized cause of tubulointerstitial lesions, and this could contribute to the development of hypertension and chronic renal failure. The aim of the present study was to evaluate a possible beneficial effect of amlodipine, a 1,4-dihydropyridine class of calcium antagonist, in a model of primary tubulointerstitial lesion produced by hyperoxaluria. Two-month-old male Sprague-Dawley rats were separated into 4 groups for a 4-week period: G1 (control; tap water only); G2 (hyperoxaluric); G3 (hyperoxaluric plus amlodipine treatment); and G4 (amlodipine treatment). G2 and G3 rats were given 1% ethylene glycol (a precursor for oxalates) in drinking water, and G3 and G4 rats were given amlodipine 2 mg. kg(-1). d(-1) by gavage. At the end of the study, we evaluated by semiquantitative scores (0 to 4) the different renal tubulointerstitial lesions, urinary albumin excretion, renal function by creatinine clearance, and blood pressure. Rats belonging to the hyperoxaluric group treated with amlodipine (G3) had fewer tubulointerstitial lesions, as follows: (1) inflammatory infiltrate score: 3.31+/-0.07 versus 0.23+/-0.12; P<0.05; (2) tubular atrophy score: 3.33+/-0.33 versus 0.50+/-0.22, P<0.05; (3) interstitial fibrosis score: 2.76+/-0.34 versus 0.31+/-0. 16, P<0.05; (4) oxalate deposits score: 3.66+/-0.33 versus 0.09+/-0. 08, P<0.05; (5) lower urinary albumin excretion (11.3+/-2 versus 27+/-4.5 mg/d, P<0.01); and (6) higher creatinine clearance (1. 22+/-0.08 versus 1.13+/-0.08, P<0.01) compared with the hyperoxaluric group untreated with amlodipine (G2). On the other hand, there were no significant changes in blood pressure in any group. In view of these data, we suggest that amlodipine, probably by nonhemodynamic mechanisms of action, can provide an important benefit in the prevention of epithelial tubular cell injury and inflammatory response and therefore in the prevention of the progressive tubulointerstitial fibrosis caused by oxalates.