TY - JOUR
T1 - Effect of losartan on renal microvasculature during chronic inhibition of nitric oxide visualized by micro-CT
AU - Fortepiani, Loudes A.
AU - Ruiz, M. Clara Ortiz
AU - Passardi, Federico
AU - Bentley, Michael D.
AU - Garcia-Estan, Joaquin
AU - Ritman, Erik L.
AU - Romero, J. Carlos
PY - 2003/11
Y1 - 2003/11
N2 - Chronic inhibition of nitric oxide (NO) synthase with the competitive L-arginine analog NG-nitro-L-arginine 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 AT1 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 AT1 receptor antagonist losartan (40 mg·kg-1·day-1 each) in their drinking water for 19 days. Kidneys from each group (control, L-NAME-, and L-NAME + 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-NAME-treated rats had significantly fewer normal glomeruli (28,824 ± 838) than those of control rats (36,266 ± 3,572). Losartan normalized the number to control values (34,094 ± 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 AT 1 receptor blockade abolished those changes, the data suggest that the reduction in vasculature is mediated by ANG II through AT1 receptors.
AB - Chronic inhibition of nitric oxide (NO) synthase with the competitive L-arginine analog NG-nitro-L-arginine 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 AT1 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 AT1 receptor antagonist losartan (40 mg·kg-1·day-1 each) in their drinking water for 19 days. Kidneys from each group (control, L-NAME-, and L-NAME + 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-NAME-treated rats had significantly fewer normal glomeruli (28,824 ± 838) than those of control rats (36,266 ± 3,572). Losartan normalized the number to control values (34,094 ± 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 AT 1 receptor blockade abolished those changes, the data suggest that the reduction in vasculature is mediated by ANG II through AT1 receptors.
KW - Angiotensin II
KW - N-nitro-L-arginine methyl ester
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U2 - 10.1152/ajprenal.00120.2003
DO - 10.1152/ajprenal.00120.2003
M3 - Article
C2 - 12837684
AN - SCOPUS:0142025384
VL - 285
SP - F852-F860
JO - American journal of physiology. Renal physiology
JF - American journal of physiology. Renal physiology
SN - 0363-6127
IS - 5 54-5
ER -