(Hypertension. 2000;35:800.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Heme Oxygenase-1 Is Upregulated in the Kidney of Angiotensin II–Induced Hypertensive Rats
Possible Role in Renoprotection
From the Department of Cardiovascular Medicine (T.A., N.I., J.-i.T., R.N., M.O.), University of Tokyo Graduate School of Medicine (Japan); Department of Pathology (I.M.), Tokai University School of Medicine, Kanagawa, Japan; and Pediatric Nephrology Laboratory (S.-S.T., J.R.I.), Massachusetts General Hospital, Boston, Mass.
Correspondence to Nobukazu Ishizaka, MD, PhD, Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail nobuishizka-tky{at}umin.ac.jp
Abstract—In this study, we investigated the regulation and physiological role of heme oxygenase-1 (HO-1) in the kidney of rats with hypertension. Rats were continuously administered either angiotensin II (Ang II) or norepinephrine with an osmotic minipump for up to 7 days. Ang II infusion decreased the glomerular filtration rate (GFR) as determined through creatinine clearance (3.2±0.2 versus 1.2±0.2 mL/min with Ang II infusion, P<0.01) and increased proteinuria (9.7±1.3 versus 28.1±7.2 mg/d with Ang II infusion, P<0.01). In contrast, norepinephrine did not alter these laboratory values. Ang II infusion significantly increased HO-1 expression in mRNA (442±98% of control at day 5, P<0.01) and protein levels (314±49% of control at day 5, P<0.01). Immunohistochemistry showed that in the kidney of normotensive rats, HO-1 was expressed mainly in the basal side in the renal tubules. After Ang II infusion, HO-1 staining was more extensively dispersed in the tubular epithelial cells. The intraperitoneal administration of zinc protoporphyrin, an HO inhibitor, to Ang II–infused rats further decreased GFR (0.8±0.1 mL/min) and increased proteinuria (52.5±13.0 mg/d). In contrast, the administration of hemin, an HO inducer, ameliorated the Ang II–induced decrease in GFR (2.4±0.2 mL/min) and increase in proteinuria (9.3±4.5 mg/d). These data suggest that HO-1 upregulation in the kidney of Ang II–induced hypertensive rats may exert a renoprotective effect against Ang II–induced renal injury.
Key Words: hypertension • angiotensin II • proteinuria • oxidative stress • kidney
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