L-ARGININE DECREASES THE INFILTRATION OF THE KIDNEY BY MACROPHAGES IN OBSTRUCTIVE NEPHROPATHY AND PUROMYCIN-INDUCED NEPHROSIS

We examined the effect of 1% L-arginine in the drinking water on the infiltration of the kidney by macrophages in rats with puromycin aminonucleoside-induced nephrosis (PAN) and in rats with bilateral ureteral obstruction (BUG) of 24 hours duration. Rats given L-arginine in the drinking water for three days before BUO or PAN was initiated had a greater glomerular filtration rate after release of BUO or induction of PAN than similar rats not given L-arginine (P < 0.0001). Administration of L-arginine decreased the renal infiltration by macrophages in rats with PAN (P < 0.0001) or BUO (P < 0.0001) compared to rats with PAN or BUO given tap water alone. Chemotaxis studies suggested that macrophages were activated during obstruction as evidenced by the greater random migration of peritoneal macrophages obtained from rats with 24-hour urethral obstruction than from sham-operated rats (SOR; P < 0.0001). In vitro, maximal chemotaxis induced by 7% zymosan-activated serum (ZAS) in peritoneal macrophages from SOR was enhanced by low (10(-6) to 10(-5) M) and decreased by high concentrations (10(-3) to 10(-2) M) of L-arginine in the incubation medium. Migration of macrophages from rats with urethral obstruction was increased by 7% ZAS but the increase diminished with high concentrations of L-arginine (10(-3) to 10(-2) M). Random migration of peritoneal macrophages obtained from rats with urethral obstruction given L-arginine prior to obstruction was significantly lower than that of peritoneal macrophages obtained from similar rats given tap water alone prior to obstruction. Plasma levels of corticosterone were greater (P < 0.002) in rats with BUO given L-arginine than in rats with BUO given tap water alone. Thus, administration of L-arginine improves renal function of rats with PAN or BUG. This may be due, at least in part, to decreased renal macrophage infiltration. L-arginine may cause this decrease in macrophage infiltration by directly inhibiting macrophage chemotaxis and by increasing the levels of circulating corticosterone.