title: Long-term treatment with nebivolol attenuates renal damage in Zucker diabetic fatty rats.
abstract: 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.
  
  
  CONCLUSIONS
  Our current finding underscores the importance of this therapy in hypertensive states concomitant with altered lipid and glucose metabolism.
authors: Laboratory of Experimental Medicine, Hospital Alemán, Buenos Aires, Argentina. jorgetoblli@fibertel.com.ar
authors: Jorge E
authors: JE
authors: Toblli
authors: Gabriel
authors: G
authors: Cao
authors: Jorge F
authors: JF
authors: Giani
authors: Marina C
authors: MC
authors: Muñoz
authors: Margarita
authors: M
authors: Angerosa
authors: Fernando P
authors: FP
authors: Dominici
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology / Q000627:therapeutic use; D001578:Benzopyrans / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000494:pharmacology / Q000627:therapeutic use*; D005355:Fibrosis; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications*; D000068577:Nebivolol; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011924:Rats, Zucker; D013997:Time Factors
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D001578:Benzopyrans; D004983:Ethanolamines; D000068577:Nebivolol; D001262:Atenolol; D005947:Glucose