LONG-TERM TREATMENT WITH NEBIVOLOL ATTENUATES RENAL DAMAGE IN ZUCKER DIABETIC FATTY RATS

TOBLLI JE, CAO G, GIANI JF, MUñOZ MC, ANGEROSA M, DOMINICI FP

JOURNAL OF HYPERTENSION

LIPPINCOTT WILLIAMS & WILKINS

Año: 2011 p. 1613 - 1623

0263-6352

OBJECTIVE: Atenolol, a first-generation â-blocker, effectively reduces blood pressure, although its use in metabolic syndrome remains controversial. Accordingly, this study evaluated the renal effects of nebivolol, a third-generation â-blocker with additional vasodilating activity, versus those of atenolol in an animal model of diabetic nephropathy. METHODS: Zucker diabetic fatty (ZDF) rats and control lean Zucker rats (LZRs) were treated for 6 months with either nebivolol or atenolol. Blood pressure, circulating insulin, triglycerides, cholesterol and glucose, as well as proteinuria and creatinine clearance were evaluated. Thiobarbituric acid-reactive species, reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, CuZn superoxide dismutase, catalase and glutathione peroxidase were determined as biomarkers of oxidative stress in kidney homogenates. Expression of transforming growth factor-â1 (TGF-â1), á-smooth muscle actin (á-SMA), collagen type I and III, plasminogen activator inhibitor-1 (PAI-1), vascular and platelet endothelial cell adhesion molecule-1 (VCAM-1 and PECAM-1, respectively) were determined by immunohistochemistry. Fibrosis was evaluated by light microscopy. RESULTS: Both drugs induced a similar control of blood pressure throughout the study. Contrary to atenolol, nebivolol showed a beneficial impact on lipid profile, preserved glomerular filtration rate, reduced proteinuria and induced a positive regulation of structural podocyte proteins (nephrin and podocin) expression. Additionally nebivolol decreased oxidative stress biomarkers, induced a substantial reduction in the accumulation of extracellular matrix proteins, down-regulated the renal expression of VCAM-1, monocyte chemotactic protein-1 (MCP-1), ED1, á-SMA, TGF-â1 and PAI-1 and up-regulated the expression of PECAM-1. CONCLUSION: Our current finding underscores the importance of this therapy in hypertensive states concomitant with altered lipid and glucose metabolism