Effects of thiol antioxidant on reduced nicotinamide adenine dinucleotide phosphate oxidase in hypertensive Dahl salt-sensitive rats.
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(2)O(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(2)O(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.
Zhang
Ling
L
Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Fujii
Shigemoto
S
Igarashi
Junsuke
J
Kosaka
Hiroaki
H
D000109:Acetylcholine / Q000494:pharmacology; D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000652:urine; D004730:Endothelium, Vascular / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000652:urine; D006973:Hypertension / Q000201:enzymology* / Q000378:metabolism; D007678:Kidney Glomerulus / Q000166:cytology; D008297:Male; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D012965:Sodium Chloride / Q000378:metabolism / Q000633:toxicity; D013481:Superoxides / Q000032:analysis / Q000378:metabolism; D013929:Thromboxane B2 / Q000097:blood / Q000652:urine; D015854:Up-Regulation
D000975:Antioxidants; D013481:Superoxides; C075750:8-epi-prostaglandin F2alpha; D012965:Sodium Chloride; D013929:Thromboxane B2; D015237:Dinoprost; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases; D000109:Acetylcholine; D000111:Acetylcysteine