THE EFFECTS OF A HIGH-SALT DIET ON GENE-EXPRESSION OF NA+ H+ EXCHANGER AND GROWTH-FACTORS IN 5/6-NEPHRECTOMIZED RATS/

The effects of a high salt diet on renal destruction and the therapeut ic effects of amiloride (Na+/H+ exchanger inhibitor) and furosemide (N a+K+/2Cl(-) exchanger inhibitor) were examined in 5/6-nephrectomized r ats fed a high salt diet. A simultaneous analysis of the effects of a high salt intake on the renal expression of Na+/H+ exchanger-1 (NHE-1) , transforming growth factor-beta 1 (TGF-beta 1) or platelet-derived g rowth factor-B (PDGF-B) mRNA was performed in this model. The 5/6-neph rectomized Sprague-Dawley rats were given a diet containing 8 or 1% so dium chloride for 5 weeks. This high salt diet accelerated the elevati on of blood pressure and aggravated both glomerulosclerosis and inters titial fibrosis in 5/6-nephrectomized rats. The daily administration o f amiloride was found to be protective against the elevation of blood pressure, glomerular hypertrophy and the aggravation of renal histolog y which were induced by a high salt diet. The expression of TGF-beta 1 and PDGF-B mRNA was up-regulated by a high salt diet, but the express ion of NHE-1 mRNA was not. The overexpression of TGF-beta 1 and PDGF-B mRNA was reduced by the daily administration of amiloride but not by furosemide. In conclusion, the destructive effects of a high salt diet on the kidneys may be mediated through hypertension, glomerular hyper trophy and the overexpression of the growth factors. Amiloride may thu s be more protective for high salt induced renal aggravation than furo semide, although the expression of NHE-1 mRNA did not show any substan tial increase due to a high salt diet.