Heme oxygenase-1 is upregulated in the kidney of angiotensin II-induced hypertensive rats - Possible role in renoprotection

In this study, we investigated the regulation and physiological role of hem e oxygenase-1 (HO-1) in the kidney of rats with hypertension. Rats were con tinuously administered either angiotensin II (Ang II) or norepinephrine wit h an osmotic minipump for up to 7 days. Ang II infusion decreased the glome rular 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 con trol 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 A ng II infusion, HO-1 staining was more extensively dispersed in the tubular epithelial cells. The intraperitoneal administration of zinc protoporphyri n, 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 ad ministration of hemin, an HO inducer, ameliorated the Ang II-induced decrea se 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 h ypertensive rats may exert a renoprotective effect against Ang II-induced r enal injury.