1. The present study was designed to assess whether glomerular expression of mRNAs for endothelin-1 and endothelin-3, as well as endothelin receptors A and B is affected by a low-protein diet during the course of focal glomerular sclerosis.
2. Focal glomerular sclerosis was induced in rats by injection of puromycin aminonucleoside on days 0, 27, 34 and 41 in conjunction with unilateral nephrectomy on day 22. Control rats were subjected to nephrectomy or sham operation on day 22.
3. Animals were divided into six groups. In group 1, the puromycin aminonucleoside-injected rats were fed a standard diet containing 22% protein. In group 2, the puromycin aminonucleoside-injected rats were fed a low-protein diet containing 6% protein, which was initiated on the day of the first puromycin aminonucleoside injection. In group 3, the nephrectomized rats without puromycin aminonucleoside were fed a standard diet. In group 4, the nephrectomized rats without puromycin aminonucleoside were fed a low-protein diet. In group 5, the sham-operated rats were fed a standard diet. In group 6, the sham-operated rats were fed a low-protein diet.
4. The percentage of sclerotic glomeruli in group 1 rats increased markedly with time, reaching 77% on day 80.
5. The glomerular mRNA levels for endothelin-1 and endothelin receptors A and B increased significantly as glomerular sclerosis progressed, whereas no endothelin-3 mRNA was detected in the glomeruli of any group.
6. The endothelin-1 production in isolated glomeruli from group 1 increased significantly as glomerular sclerosis progressed.
7. In group 2, the low-protein diet reduced the prevalence of glomerular sclerosis, attenuated the rise in mRNA levels for endothelin-1 and endothelin receptors A and B and reduced endothelin-1 production in glomeruli from rats with focal glomerular sclerosis.
8. These data indicate that increases in glomerular endothelin-1 and endothelin receptor mRNA levels are associated with the development of puromycin aminonucleoside-induced glomerular sclerosis. These effects are blunted by administration of a low-protein diet.