Abstract: To evaluate whether N-nitro-L-arginine methylester （L-NAME ） can exacerbate nephrovsclerosis in spontaneously hypertensive rats （SHR），SHR were randomly divided into two groups according to their body weight. Group Ⅰ （SHR, n = 10） were given tap-water, while Group Ⅱ （SHR+NAME,n=9） were received L-NAME in the drinking water （50 mg/L）.Twenty-four-hour urine samples were collected at baseline，weeks 2 and 4 after the start of L-NAME for proteinuria determination. Cardiac hemodynamic and renal clearance experiments were performed after the last 24 h urine collection. The severity of the renal injury was semi-quantitatively assessed. The results showed that the L-NAME in duced significant increases in mean arterial blood pressure and left ventricular end-diastolic prevssure at the end of the treatment ,but had little effects on heart rate and the maximal rate of rise of LV pressure （dP/dtmax）. It also induced significant rises in the ratios of heart weight/body weight and left ventricle weight/body weight. In the kidney, L-NAME induced a progressive increases in proteinuria. It caused a profound elevation in renal vascular resistance, leading to a marked decrease in renal plasma flow, but a proportionately lesser decline in GFR. Thus, the filtration fraction rose. Se-mi-quantitative histological lesion grading revealed severe tubulointerstitial and renal vascular lesions,along with very mild glomerular sclerosis in SHR treated with L-NAME. Our results suggest that L-NAME exacerbated nephrosclerosis in SHR.Young SHR treated with L-NAME can he used as a model of chronic renal failure.

Key words: N-nitro-L-arginine methylester, Spontaneously hypertensive rats, Cardiac hemody-ncimics, Renal vascular resistance, Nephrosclerosis