Heme Oxygenase-1 Is Upregulated in the Kidney of Angiotensin II–Induced Hypertensive Rats

Abstract

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.