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

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.

• Authors: T Aizawa, N Ishizaka, J i Taguchi, R Nagai, I Mori, S S Tang, J R Ingelfinger, M Ohno
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 35 Issue 3 Pg. 800-6 (Mar 2000) ISSN: 1524-4563 [Electronic] United States
• PMID: 10720598 (Publication Type: Journal Article)

Chemical References

• Antihypertensive Agents
• Enzyme Inhibitors
• Protoporphyrins
• RNA, Messenger
• Vasoconstrictor Agents
• Vasodilator Agents
• Angiotensin II
• zinc protoporphyrin
• Hydralazine
• Hemin
• Heme Oxygenase (Decyclizing)
• Heme Oxygenase-1
• Losartan
• Norepinephrine

Topics

• Angiotensin II (pharmacology)
• Animals
• Antihypertensive Agents (pharmacology)
• Blood Pressure (drug effects)
• Cell Line, Transformed
• Disease Models, Animal
• Enzyme Inhibitors (pharmacology)
• Gene Expression Regulation, Enzymologic (drug effects)
• Glomerular Filtration Rate (drug effects)
• Heart Rate (drug effects)
• Heme Oxygenase (Decyclizing) (analysis, genetics, metabolism)
• Heme Oxygenase-1
• Hemin (pharmacology)
• Hydralazine (pharmacology)
• Hypertension (chemically induced, metabolism)
• Immunohistochemistry
• Kidney Tubules, Proximal (cytology, enzymology)
• Losartan (pharmacology)
• Norepinephrine (pharmacology)
• Oxidative Stress (drug effects)
• Proteinuria (chemically induced, metabolism)
• Protoporphyrins (pharmacology)
• RNA, Messenger (analysis)
• Rats
• Rats, Sprague-Dawley
• Vasoconstrictor Agents (pharmacology)
• Vasodilator Agents (pharmacology)