Increased expression of Na+/H+ exchanger in the injured renal tissues of focal glomerulosclerosis in rats

Increased expression of Na+/H+ exchanger in the injured renal tissues of focal glomerulosclerosis in rats. The renal mRNA expression of Na+/H+ exchanger (NHE) and the effects of NHE inhibitor, amiloride, on renal injury were investigated in adriamycin (ADR)-induced glomerulosclerosis model in rats, which progressively developed extensive glomerulosclerosis and interstitial fibrosis. NHE-1 mRNA from the cortex of the ADR rats progressively increased at weeks 4 and 8 and then peaked at week 16, which paralleled with the degree of glomerular sclerosis and interstitial fibrosis. The interstitial fibrosis in the ADR-rats was prevented by a daily administration of amiloride. A simultaneous analysis of the effects of a high salt diet on NHE-1 mRNA expression or renal injury was performed in the ADR rats at weeks 2 and 8. Renal or glomerular hypertrophy was observed in the control or ADR rats fed an 8% NaCl diet at week 2 and 8 compared to a 1% NaCl diet, while the NHE-1 mRNA expression was not up-regulated by an 8% NaCl diet at week 2. At week 8, the NHE-1 mRNA expression or glomerulosclerosis and interstitial fibrosis were enhanced in the ADR rats fed an 8% NaCl diet compared to a 1% NaCl diet. This histological aggravation by an 8% NaCl diet was prevented by a dairy administration of amiloride but not by furosemide. In conclusion, the increased NHE-1 mRNA expression and the preventive effects of amiloride on the renal lesions suggest a potential importance of NHE in the progressive process of ADR-nephropathy. The high salt diet had a hypertrophic and destructive effect on kidney or glomeruli in the ADR rats. The hypertrophic effect of a high salt diet did not seem to be mediated through NHE activation.