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.
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.
Authors: Monique Marques da Silva; Moisés Felipe Pereira Gomes; Elizabeth de Orleans Carvalho de Moura; Mariana Matera Veras; Melina Chiemi Kubota; Ana Paula Takano; Ana Carolina Cardoso Dos Santos; Carolina Gonçalves Dos Reis José; Graziele Aparecida da Silva Souza; Naiara Magalhães Cardoso; Debora Estadella; Rafael Herling Lambertucci; Alessandra Medeiros Journal: PLoS One Date: 2022-06-03 Impact factor: 3.752
Authors: Mariana Moura Nascimento; Desiree Rita Denelle Bernardo; Ana Carolina de Bragança; Maria Heloisa Massola Shimizu; Antonio Carlos Seguro; Rildo Aparecido Volpini; Daniele Canale Journal: Front Med (Lausanne) Date: 2022-08-04
Authors: Jorge Eduardo Toblli; Carlos Rivas; Gabriel Cao; Jorge Fernando Giani; Felix Funk; Lee Mizzen; Fernando Pablo Dominici Journal: Chemother Res Pract Date: 2014-04-30