title: Angiotensin II and oxidative stress in Dahl Salt-sensitive rat with heart failure.
abstract: Reactive oxygen species have an important pathogenic role in organ damage. We investigated the role of oxidative stress via nicotinamide adenine dinucleotide phosphate (NAD[P]H) oxidase in the kidney of the Dahl salt-sensitive (DS) rats with heart failure (DSHF). Eleven-week-old DS rats fed an 8%-NaCl diet received either vehicle or imidapril (1 mg/kg per day) for 7 weeks. The renal expression of the NAD(P)H oxidase p47phox and endothelial NO synthase were evaluated. In DSHF rats, associated with increased renal angiotensin II, mRNA and protein expression of NAD(P)H oxidase p47phox were enhanced with an increase in renal lipid peroxidation production (0.33+/-0.03 versus 0.22+/-0.01 nmol/mg protein, P<0.05) and urinary excretion of hydrogen peroxide (26.9+/-6.6 versus 9.5+/-2.1 U/mg creatinine, P<0.01) compared with levels in Dahl salt-resistant rats. The endothelial NO synthase expression was decreased in the kidney. Treatment with imidapril reduced renal angiotensin II and NAD(P)H oxidase expression and the oxidative products (kidney lipid peroxidation product: 0.16+/-0.02, P<0.001; urinary hydrogen peroxide: 3.1+/-0.2, P<0.01 versus DSHF rats). Imidapril significantly decreased albuminuria and reduced glomerulosclerosis without changes in the blood pressure. In conclusion, DSHF rats showed increased oxidative stress in the kidney via NAD(P)H oxidase. Blockade of local angiotensin II with subpressor dose of imidapril inhibited NAD(P)H oxidase and prevented renal damage.
authors.affiliation: Division of Nephrology and Endocrinology, Department of Internal Medicine, University of Tokyo, Tokyo, Japan. tojyo-2im@h.u-tokyo.ac.jp
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tojo
authors.forename: Maristela Lika
authors.initials: ML
authors.lastname: Onozato
authors.forename: Naohiko
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Atsuo
authors.initials: A
authors.lastname: Goto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsuoka
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fujita
mesh_terms: D000419:Albuminuria / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D006333:Heart Failure / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000652:urine; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; D010750:Phosphoproteins; D012333:RNA, Messenger; D000804:Angiotensin II; D006861:Hydrogen Peroxide; C065166:imidapril; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1