on October 14, 2002
Published online before print October 14, 2002, doi: 10.1161/01.HYP.0000039506.43589.D5
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Submitted on July 1, 2002
From the Division of Nephrology and Endocrinology, University of Tokyo (A.T., M.L.O., A.G., T.F.), Tokyo, Japan; and the Division of Hypertension and Cardiorenal Medicine, Dokkyo University School of Medicine (N.K., H.M.), Tochigi, Japan. * To whom correspondence should be addressed. E-mail: tojyo-2im{at}h.u-tokyo.ac.jp.
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.
Revised on July 24, 2002
Angiotensin II and Oxidative Stress in Dahl Salt-Sensitive Rat With Heart Failure
Akihiro Tojo*;
Key words: heart failure • nitric oxide synthase • angiotensin-converting enzyme • rats, Dahl • angiotensin II
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