TY - JOUR
T1 - Kidney damage after renal ablation is worsened in endothelial nitric oxide synthase (-/-) mice and improved by combined administration of L-arginine and antioxidants
AU - Mendoza, Monica G.Arellano
AU - Castillo-Henkel, Carlos
AU - Medina-Santillan, Roberto
AU - Jarillo Luna, R. Adriana
AU - Robles, Hilda Vargas
AU - Romo, Eunice
AU - Rios, Amelia
AU - Escalante, Bruno
PY - 2008/4
Y1 - 2008/4
N2 - Aim: Reduction in nitric oxide (NO) levels during kidney failure has been related to the reaction of NO with superoxide anions to yield peroxynitrite which possesses the biological activity responsible for renal damage. However, stimulation of the NO pathway ameliorates the progression of kidney failure. Thus, it is unclear whether NO prevents or acts as the compound responsible for the cytotoxicity observed during kidney failure. Methods: We evaluated the development of kidney failure in animals that were wild type and deficient in endothelial NO synthase (eNOS (-/-)) and tested the effects of an antioxidant treatment and NO precursors on the generation of superoxide anion and kidney failure parameters. Results: In wild-type mice, five-sixths nephrectomy increased proteinuria from 3.0 ± 0.35 to 14.5 ± 0.76 mg protein/24 h (P < 0.05), blood pressure from 83.1 ± 1.8 to 126.6 ± 1.7 mmHg (P < 0.05), and superoxide production from 1.4 ± 0.6% to 74.3 ± 0.8% (P < 0.05). The effects of five-sixths nephrectomy on the eNOS (-/-) mice were greater compared with wild-type mice. Proteinuria increased from 6.7 ± 0.5 to 22.7 ± 2.0 mg protein/24 h (P < 0.05), blood pressure increased from 93.3 ± 0.9 to 151.2 ± 3.4 mmHg (P < 0.05), and superoxide production increased from 12.9 ± 0.5% to 99.8 ± 1.3% (P < 0.05). The nitrotyrosine levels were lower in eNOS (-/-) mice as compared to wild-type mice. A combination of L-arginine and antioxidant treatment ameliorated renal damage. The effect was improved in wild-type animals. Conclusion: Our data support the relevance of NO as an antagonist to superoxide in renal tissues and suggest that the loss of this mechanism promotes the progression of kidney failure.
AB - Aim: Reduction in nitric oxide (NO) levels during kidney failure has been related to the reaction of NO with superoxide anions to yield peroxynitrite which possesses the biological activity responsible for renal damage. However, stimulation of the NO pathway ameliorates the progression of kidney failure. Thus, it is unclear whether NO prevents or acts as the compound responsible for the cytotoxicity observed during kidney failure. Methods: We evaluated the development of kidney failure in animals that were wild type and deficient in endothelial NO synthase (eNOS (-/-)) and tested the effects of an antioxidant treatment and NO precursors on the generation of superoxide anion and kidney failure parameters. Results: In wild-type mice, five-sixths nephrectomy increased proteinuria from 3.0 ± 0.35 to 14.5 ± 0.76 mg protein/24 h (P < 0.05), blood pressure from 83.1 ± 1.8 to 126.6 ± 1.7 mmHg (P < 0.05), and superoxide production from 1.4 ± 0.6% to 74.3 ± 0.8% (P < 0.05). The effects of five-sixths nephrectomy on the eNOS (-/-) mice were greater compared with wild-type mice. Proteinuria increased from 6.7 ± 0.5 to 22.7 ± 2.0 mg protein/24 h (P < 0.05), blood pressure increased from 93.3 ± 0.9 to 151.2 ± 3.4 mmHg (P < 0.05), and superoxide production increased from 12.9 ± 0.5% to 99.8 ± 1.3% (P < 0.05). The nitrotyrosine levels were lower in eNOS (-/-) mice as compared to wild-type mice. A combination of L-arginine and antioxidant treatment ameliorated renal damage. The effect was improved in wild-type animals. Conclusion: Our data support the relevance of NO as an antagonist to superoxide in renal tissues and suggest that the loss of this mechanism promotes the progression of kidney failure.
KW - Kidney failure
KW - L-arginine
KW - Nitric oxide
KW - Reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=40349089601&partnerID=8YFLogxK
U2 - 10.1111/j.1440-1797.2007.00897.x
DO - 10.1111/j.1440-1797.2007.00897.x
M3 - Artículo
C2 - 18315704
SN - 1320-5358
VL - 13
SP - 218
EP - 227
JO - Nephrology
JF - Nephrology
IS - 3
ER -