DIETARY SUPPLEMENTATION WITH L-ARGININE LIMITS CELL-PROLIFERATION IN THE REMNANT GLOMERULUS

One effect of L-arginine is to increase nitric oxide (NO) production b y endothelial cells. NO directly reduces endothelin-l production by en dothelial cells and also inhibits platelet-derived growth factor (PDGF ) induced cell proliferation. Since subtotal renal ablation is associa ted with an early phase of cell proliferation in the glomerulus that p recedes injury, we examined the effect of dietary supplementation with L-arginine on glomerular cell proliferation and expression of the cyt okine endothelin-1 (ET-1). A first group of renal-ablated rats was unt reated. A second group of renal-ablated rats received L-arginine (1%) in the drinking water. Two weeks after subtotal ablation renal cortica l tissue was snap frozen for immunohistochemical analysis for prolifer ating cell nuclear antigen (PCNA) expression and ET-1. Protein and tot al RNA was extracted from sieved glomeruli. mRNA levels were quantitat ed by co-amplification RT-PCR utilizing specific 5' and 3' primers for rat ET-1 and beta-actin. L-arginine reduced the number of PCNA positi ve nuclei in remnant glomeruli, and Western blot Analysis of glomerula r proteins also showed that L-arginine reduced PCNA expression. Glomer ular ET-1 mRNA levels and protein immunostaining declined in the rats receiving L-arginine. We conclude that dietary supplementation with L- arginine reduces early cell proliferation in the remnant glomerulus, a n effect that may be mediated, in part, by a decrease in ET-1 producti on.