Decreased renal heme oxygenase-1 expression contributes to decreased renal function during cirrhosis
| Autor: | Motoaki Miyazono, Ethan P. Carter, Kenneth G. Morris, Chrystelle Garat |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Liver Cirrhosis
Male medicine.medical_specialty Cirrhosis Nitric Oxide Synthase Type III Physiology Biliary cirrhosis Renal function Kidney Nitric Oxide Renal Circulation Rats Sprague-Dawley chemistry.chemical_compound Internal medicine medicine Animals Carbon Monoxide business.industry Body Weight Zinc protoporphyrin medicine.disease Immunohistochemistry Rats Heme oxygenase medicine.anatomical_structure Endocrinology chemistry Renal blood flow Heme Oxygenase (Decyclizing) Nitric Oxide Synthase business Heme Oxygenase-1 Glomerular Filtration Rate Kidney disease |
| Zdroj: | American Journal of Physiology-Renal Physiology. 283:F1123-F1131 |
| ISSN: | 1522-1466 1931-857X |
| DOI: | 10.1152/ajprenal.00363.2001 |
| Popis: | Heme oxygenase (HO) is the rate-limiting enzyme in the degradation of heme, catalyzing the oxidative cleavage of heme molecules to biliverdin, carbon monoxide, and iron. The present study was designed to investigate the role of HO-1 in the pathogenesis of renal dysfunction during cirrhosis. Biliary cirrhosis was induced in rats by common bile duct ligation (CBDL). Animals were studied 2 and 5 wk after surgery. In kidney from CBDL rats, HO-1 protein expression increased slightly at 2 wk but was abolished at 5 wk. In addition, we confirmed histologically that HO-1 expression was suppressed in renal tubules and interlobular arterioles in 5-wk-old CBDL rats. Conversely, HO-1 expression in liver was strongly increased. Consistent with the development of cirrhosis and renal dysfunction mean arterial pressure (MAP), glomerular filtration rate (GFR), and renal blood flow (RBF) were decreased in CBDL rats compared with sham-operated controls. In sham rats, treatment with the selective HO inhibitor zinc protoporphyrin markedly decreased GFR and RBF to values similar to those measured in CBDL rats without decreasing MAP. In conclusion, decreased renal HO-1 expression contributes to deteriorated renal function and hemodynamics during cirrhosis. This finding provides a novel mechanism for the pathophysiology of renal dysfunction during cirrhosis. |
| Databáze: | OpenAIRE |
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