G -nitro-Larginine methyl ester (L-NAME) leads to an elevated systemic blood pressure and reduction in renal blood flow without significant changes in urinary sodium and water excretion. Simultaneous administration of ANG II AT 1 receptor antagonist losartan and L-NAME prevents the alterations in blood pressure and renal hemodynamics. Microcomputed tomography (micro-CT) was used to investigate the role of ANG II in the changes of renal microvasculature during chronic NO inhibition. Sprague-Dawley rats were given L-NAME with or without AT 1 receptor antagonist losartan (40 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 each) in their drinking water for 19 days. Kidneys from each group (control, L-NAME-, and L-NAME ϩ losartan-treated rats) were perfusion-fixed in situ, infused with a silicon-based polymer containing lead chromate, and scanned by micro-CT. The microvasculature in the reconstructed three-dimensional renal images was studied using computerized analytic techniques. Kidneys of L-NAMEtreated rats had significantly fewer normal glomeruli (28,824 Ϯ 838) than those of control rats (36,266 Ϯ 3,572). Losartan normalized the number to control values (34,094 Ϯ 1,536). The amount of vasculature in the cortex, outer medulla, and inner medulla of L-NAME-treated rats was about two-thirds that of control rats; losartan normalized the values to control levels. These data indicate that chronic treatment with the NO synthase inhibitor L-NAME produces a generalized rarefaction of renal capillaries. Because simultaneous AT1 receptor blockade abolished those changes, the data suggest that the reduction in vasculature is mediated by ANG II through AT 1 receptors. NG -nitro-L-arginine methyl ester; angiotensin II NITRIC OXIDE (NO) is a physiologically important vasodilator, which plays a major role in the regulation of systemic and renal hemodynamics (16). Chronic inhibition of NO synthesis produces a general vasoconstriction that leads to an increased blood pressure and impairment of renal function including decreased renal blood flow (RBF) and glomerular filtration rate (GFR) without significant changes in urinary sodium and water excretion (3,11,30). Besides the functional changes, the inhibition of NO synthesis produces renal vascular damage including glomerulosclerosis, ischemia, necrosis, and increased interstitium (12, 24). The mechanism underlying the effect of NO synthesis inhibition is not completely understood, but it is likely that the renin-angiotensin system is responsible for the renal and systemic alterations induced by the chronically reduced NO bioavailability. For instance, the simultaneous blockade of NO synthesis and ANG II AT 1 receptor prevents the hypertension, renal functional and morphological consequences of the inhibition of NO synthesis alone (35). Ohishi et al. (20) found that the blockade of ANG II AT 1 receptors attenuated the vasoconstriction elicited by the inhibition of NO synthesis in juxtamedullary afferent and efferent arterioles perfused in vitro. In vivo experiments (23) showed that NO modulated the ANG II re...