Renal ischemia-reperfusion injury is prevented by the mineralocorticoid receptor blocker spironolactone
Autor: | Juan M. Mejia-Vilet, Norma A. Bobadilla, Norma Uribe, Victoria Ramírez, Cristino Cruz, Gerardo Gamba |
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Rok vydání: | 2007 |
Předmět: |
Male
medicine.medical_specialty Endothelium Physiology Urinary system Blotting Western Urology Spironolactone chemistry.chemical_compound Mineralocorticoid receptor Malondialdehyde Internal medicine In Situ Nick-End Labeling Animals Medicine Rats Wistar Aldosterone Mineralocorticoid Receptor Antagonists Glutathione Peroxidase biology Renal ischemia Superoxide Dismutase business.industry Catalase medicine.disease Immunohistochemistry Rats Nitric oxide synthase medicine.anatomical_structure Endocrinology chemistry Vasoconstriction Apoptosis Reperfusion Injury biology.protein RNA Kidney Diseases Lipid Peroxidation business Kidney disease |
Zdroj: | American Journal of Physiology-Renal Physiology. 293:F78-F86 |
ISSN: | 1522-1466 1931-857X |
Popis: | Renal ischemia and reperfusion (I/R) injury is the major cause of acute renal failure and may also be involved in the development and progression of some forms of chronic kidney disease. We previously showed that a mineralocorticoid receptor (MR) blockade prevents renal vasoconstriction induced by cyclosporine that leads to acute and chronic renal failure (Feria I, Pichardo I, Juarez P, Ramirez V, Gonzalez MA, Uribe N, Garcia-Torres R, Lopez-Casillas F, Gamba G, Bobadilla NA. Kidney Int 63: 43–52, 2003; Perez-Rojas JM, Derive S, Blanco JA, Cruz C, Martinez de la Maza L, Gamba G, Bobadilla NA. Am J Physiol Renal Physiol 289: F1020–F1030, 2005). Thus we investigated whether spironolactone administration prevents the functional and structural damage induced by renal ischemia-reperfusion (I/R). Five groups were studied: sham-operated animals, rats that underwent 20 min of ischemia and 24 h of reperfusion, and three groups that received spironolactone 1, 2, or 3 days before I/R, respectively. Renal I/R produced significant renal dysfunction and tubular damage. Spironolactone administration completely prevented a decrease in renal blood flow, the development of acute renal failure, and tubular apoptosis. The protection conferred by spironolactone was characterized by decreasing oxidative stress, as evidenced by a reduction in kidney lipoperoxidation, increasing expression of antioxidant enzymes, and restoration of urinary NO2/NO3 excretion. Endothelial nitric oxide synthase expression was upregulated by a mineralocorticoid receptor blockade in I/R groups; in addition, an increase in activating phosphorylation of this enzyme at residue S1177 and a decrease in inactivating phosphorylation at T497 were observed. In conclusion, our study shows that spironolactone administration prevents the renal injury induced by I/R, suggesting that aldosterone plays a central role in this model of renal injury. |
Databáze: | OpenAIRE |
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