Nebivolol Attenuates Redox-Sensitive Glomerular and Tubular Mediated Proteinuria in Obese Rats

摘要: Obesity and insulin resistance-related proteinuria is associated with oxidative stress impaired tissue bioavailable nitric oxide. Recent data suggest that nicotinamide adenine dinucleotide phosphate oxidase-mediated injury to the proximal tubule, like seen in glomerulus, contributes insulin-resistant states. The vasodilator β-blocker nebivolol reduces oxidase activity, increases oxide, improves sensitivity. To test hypothesis a treatment strategy attenuates obesity-associated glomerular tubule derived protein, we treated young Zucker obese (ZO) age-matched lean male rats (10 mg · kg−1 d−1) for 21 d. Compared lean, ZO controls exhibited increased γ-glutamyl transpeptidase, reductions systemic sensitivity association renal renin, (pro)renin receptor, angiotensin II type 1 mineralocorticoid receptor immunostaining, stress, tubular structural abnormalities were substantially improved vivo treatment. Nebivolol also led improvements podocyte foot-process effacement improvement podocyte-specific proteins (nephrin synaptopodin) as well tubule-specific (megalin lysosomal-associated membrane protein-2) ultrastructural remodeling kidney. Our findings support notion obesity resistance lead glomerulotubular resultant sources of excess urine protein. Furthermore, results this study beneficial effect on was from weight state resistance.