OBJECTIVE

Atenolol, a first-generation β-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 β-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-β1 (TGF-β1), α-smooth muscle actin (α-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, α-SMA, TGF-β1 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.