TY - JOUR
T1 - Effects of thiol antioxidant on Reduced Nicotinamide Adenine Dinucleotide Phosphate oxidase in hypertensive Dahl salt-sensitive rats
AU - Zhang, Ling
AU - Fujii, Shigemoto
AU - Igarashi, Junsuke
AU - Kosaka, Hiroaki
N1 - Funding Information:
This research was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
PY - 2004/12/1
Y1 - 2004/12/1
N2 - Recent studies implicate of reactive oxygen species (ROS) in hypertension; however, whether reactive oxygen species promote hypertensive derangements is not fully clear. We thus investigated the effects of an antioxidant, n-acetyl-l-cysteine, on hypertensive Dahl salt-sensitive rats. High-salt intake for 4 weeks markedly elevated systolic arterial pressure, urinary excretion of protein, 8-isoprostane, and H 2O 2, and the enzyme activity of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase along with the elevated expression of its subunits gp91phox and p47phox at the levels of mRNA and protein. Supplement with n-acetyl-l-cysteine reduced the increase in systolic arterial pressure and counteracted the elevation of urinary excretion of protein, 8-isoprostane, and H 2O 2, and the increases in NADPH oxidase activity/expression in high-salt-loaded Dahl salt-sensitive rats. n-acetyl-l-cysteine supplement ameliorated plasma and urinary levels of thromboxane B 2 (an end metabolite of thromboxane A 2), associated with improvement of both the abnormal contraction and the impaired nitric oxide-dependent relaxation in renal arteries. These results revealed that oxidative stress mediates hypertensive changes in Dahl salt-sensitive rats, because thiol antioxidant n-acetyl-l-cysteine attenuated the augmentation of local ROS production by diminishing the elevation of NADPH oxidase expression and ameliorated renal/vascular hypertensive changes.
AB - Recent studies implicate of reactive oxygen species (ROS) in hypertension; however, whether reactive oxygen species promote hypertensive derangements is not fully clear. We thus investigated the effects of an antioxidant, n-acetyl-l-cysteine, on hypertensive Dahl salt-sensitive rats. High-salt intake for 4 weeks markedly elevated systolic arterial pressure, urinary excretion of protein, 8-isoprostane, and H 2O 2, and the enzyme activity of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase along with the elevated expression of its subunits gp91phox and p47phox at the levels of mRNA and protein. Supplement with n-acetyl-l-cysteine reduced the increase in systolic arterial pressure and counteracted the elevation of urinary excretion of protein, 8-isoprostane, and H 2O 2, and the increases in NADPH oxidase activity/expression in high-salt-loaded Dahl salt-sensitive rats. n-acetyl-l-cysteine supplement ameliorated plasma and urinary levels of thromboxane B 2 (an end metabolite of thromboxane A 2), associated with improvement of both the abnormal contraction and the impaired nitric oxide-dependent relaxation in renal arteries. These results revealed that oxidative stress mediates hypertensive changes in Dahl salt-sensitive rats, because thiol antioxidant n-acetyl-l-cysteine attenuated the augmentation of local ROS production by diminishing the elevation of NADPH oxidase expression and ameliorated renal/vascular hypertensive changes.
KW - Dahl
KW - Free radicals
KW - Hydrogen peroxide
KW - NAC
KW - NADPH oxidase
KW - ROS
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U2 - 10.1016/j.freeradbiomed.2004.08.019
DO - 10.1016/j.freeradbiomed.2004.08.019
M3 - Article
C2 - 15528040
AN - SCOPUS:7444232157
VL - 37
SP - 1813
EP - 1820
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
IS - 11
ER -