Long-term treatment with nebivolol attenuates renal damage in Zucker fatty rats.

TOBLLI JE; CAO G; GIANI JF; MUÑOZ MC; ANGEROSA M; DOMINICI FP

JOURNAL OF HYPERTENSION

LIPPINCOTT WILLIAMS & WILKINS

Año: 2011 vol. 29 p. 1613 - 1623

0263-6352

Objective Atenolol, a first-generation b-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 b-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-b1 (TGF-b1), a-smooth muscle actin (a-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 bloodpressure 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 extracellularmatrix proteins, down-regulated the renal expression of VCAM-1, monocyte chemotactic protein-1 (MCP-1), ED1, a-SMA, TGF-b1 and PAI-1 and up-regulated the expressionof PECAM-1. Conclusion Our current finding underscores the importance of this therapy in hypertensive states concomitant with altered lipid and glucose metabolism. J Hypertens 29:1613?1623 Q 2011