Aim To compare the different effects of perindopril and losartan on kidney,and investigate the mechanisms of protective roles of these two drugs.Methods The investigation comprised normotensive control,hypertensive group,perindopril group and losartan group,of which blood pressure,nitric oxide(NO)level,microalbuminuria,renal function and relevant ultrastructural indexes in vessel and glomerulus with transmission electronic microscope were acquired.Results In three-month old hypertensive rats,electronic microscopic observation demonstrated early impairment of vessel endothelium and slight lesion of glomerular basement membrane compared with age-matched controls.Also,the hypertensive rats had lower level of renal NO and elevation of microalbuminuria.At eight-month old,aggravation of impairment of vessel endothelium and lesion of glomerulus has been shown.Microalbuminuria was associated with lesion of endothelium and glomerulus and renal NO level,but not related to blood pressure.With the treatment of perindopril or losartan,not only reduction of microalbuminuria was achieved but also elevation of NO and decrease in volume density of vessel endothelium,mesangial cells and mesangial area were shown.In addition,NO level was higher in perindopril group than that of losartan.Conclusions Endothelial dysfunction seems to be the most plausible cause of microalbuminuria in hypertension.By way of blocking Ang Ⅱ and improving endothelial function,perindopril and losartan can inhibit the deteriorations of kidney more than blood pressure lowering.Moreover,perindopril has more significant effect on elevating NO level.