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 daily 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Okuda
S
S
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Tamaki
K
K
Ando
T
T
Nagashima
A
A
Nakayama
M
M
Fukuda
K
K
Higashi
H
H
Fujishima
M
M
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000633:toxicity; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D006984:Hypertrophy; D007668:Kidney / Q000187:drug effects / Q000293:injuries / Q000378:metabolism*; D008297:Male; D015336:Molecular Probe Techniques; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012982:Sodium, Dietary / Q000008:administration & dosage; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
D012333:RNA, Messenger; D012982:Sodium, Dietary; D017923:Sodium-Hydrogen Exchangers; D000584:Amiloride; D004317:Doxorubicin