Chronic nitric oxide (NO) inhibition and salt overload (HS) promote severe hypertension and renal injury, which regress quickly, though not completely, upon treatment withdrawal. We investigated whether renal function and structure remain stable six months after ceasing these treatments. Adult male Munich-Wistar rats were distributed among 3 groups: HS, receiving 3.1% Na diet; HS+N, receiving HS and the NO inhibitor N-L-nitroarginine methylester (L-NAME), 30 mg/kg/day orally; and HS+N+L, receiving HS+N and the angiotensin II (AII) blocker, losartan (L), 50 mg/kg/day orally. In studies performed after 20 days of treatment (Protocol 1), Group HS+N exhibited severe glomerular and systemic hypertension, massive albuminuria, glomerular and interstitial injury, and infiltration by macrophages and cells expressing AII. These abnormalities were largely prevented in Group HS+N+L. A second cohort (Protocol 2) received HS+N for 20 days, followed by conventional (0.5% Na) diet and no L-NAME treatment during the subsequent 30 days. At this time, systemic and glomerular pressure, along with parameters of renal injury and inflammation, were still higher than in HS or HS+N+L, although differences were much smaller than in Protocol 1. Six months after 20-day L-NAME/salt overload treatment was ceased (Protocol 3), severe albuminuria, hypertension and renal injury developed in Group HS+N. Again, losartan prevented most of these changes. Conclusions: 1) Short-term HS+N treatment triggers the autonomous development of progressive GS; 2) This process may involve activation of the AT1 receptor; 2) Temporary HS+N treatment may represent a new model of slowly progressive chronic nephropathy.