INCREASED EXPRESSION OF NA+ H+ EXCHANGER IN THE INJURED RENAL TISSUESOF 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 ren al injury were investigated in adriamycin (ADR)-induced glomeruloscler osis model in rats, which progressively developed extensive glomerulos clerosis and interstitial fibrosis. NHE-1 mRNA from the cortex of the ADR rats progressively increased at weeks 4 and 8 and then peaked at w eek 16, which paralleled with the degree of glomerular sclerosis and i nterstitial fibrosis. The interstitial fibrosis in the ADR-rats was pr evented by a daily administration of amiloride. A simultaneous analysi s 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 glome rular hypertrophy was observed in the control or ADR rats fed an 8% Na Cl diet at week 2 and 8 compared to a 1% NaCl diet, while the NHE-1 mR NA expression was not up-regulated by an 8% NaCl diet at week 2. At we ek 8, the NHE-1 mRNA expression or glomerulosclerosis and interstitial fibrosis were enhanced in the ADR rats fed an 8% NaCl diet compared t o a 1% NaCl diet. This histological aggravation by an 8% NaCl diet was prevented by a dairy administration of amiloride but not by furosemid e. In conclusion, the increased NHE-1 mRNA expression and the preventi ve effects of amiloride on the renal lesions suggest a potential impor tance of NHE in the progressive process of ADR-nephropathy. The high s alt diet had a hypertrophic and destructive effect on kidney or glomer uli in the ADR rats. The hypertrophic effect of a high salt diet did n ot seem to be mediated through NHE activation.