CONICET | Buscador de Institutos y Recursos Humanos

de Cavanagh EM, Ferder L, Toblli JE, Piotrkowski B, Stella I, Fraga CG, Inserra F. Renal mitochondrial impairment is attenuated by AT1 blockade in experimental Type I diabetes. Am J Physiol Heart Circ Physiol 294: H456H465, 2008. First published November 16, 2007; doi:10.1152/ajpheart.00926.2007.To investigate whether ANG II type 1 (AT1) receptor blockade could protect kidney mitochondria in streptozotocin-induced Type 1 diabetes, we treated 8-wk old male Sprague-Dawley rats with a single streptozotocin injection (65 mg/kg ip; STZ group), streptozotocin and drinking water containing either losartan (30 mgkg1 day1; STZLos group) or amlodipine (3 mgkg1 day1; STZAmlo group), or saline (intraperitoneally) and pure water (control group). Four-month-long losartan or amlodipine treatments started 30 days before streptozotocin injection to improve the antioxidant defenses. The number of renal lesions, plasma glucose and lipid levels, and proteinuria were higher and creatinine clearance was lower in STZ and STZAmlo compared with STZLos and control groups. Glycemia was higher in STZLos compared with control. Blood pressure, basal mitochondrial membrane potential and mitochondrial pyruvate content, and renal oxidized glutathione levels were higher and NADH/cytochrome c oxidoreductase activity was lower in STZ compared with the other groups. In STZ and STZAmlo groups, mitochondrial H2O2 production rate was higher and uncoupling protein-2 content, cytochrome c oxidase activity, and renal glutathione level were lower than in STZLos and control groups. Mitochondrial nitric oxide synthase activity was higher in STZAmlo compared with the other groups. Mitochondrial pyruvate content and H2O2 production rate negatively contributed to electron transfer capacity and positively contributed to renal lesions. Uncoupling protein-2 content negatively contributed to mitochondrial H2O2 production rate and renal lesions. Renal glutathione reduction potential positively contributed to mitochondria electron transfer capacity. In conclusion, AT1 blockade protects kidney mitochondria and kidney structure in streptozotocin-induced diabetes independently of blood pressure and glycemia. Renal mitochondrial impairment is attenuated by AT1 blockade in experimental Type I diabetes. Am J Physiol Heart Circ Physiol 294: H456H465, 2008. First published November 16, 2007; doi:10.1152/ajpheart.00926.2007.To investigate whether ANG II type 1 (AT1) receptor blockade could protect kidney mitochondria in streptozotocin-induced Type 1 diabetes, we treated 8-wk old male Sprague-Dawley rats with a single streptozotocin injection (65 mg/kg ip; STZ group), streptozotocin and drinking water containing either losartan (30 mgkg1 day1; STZLos group) or amlodipine (3 mgkg1 day1; STZAmlo group), or saline (intraperitoneally) and pure water (control group). Four-month-long losartan or amlodipine treatments started 30 days before streptozotocin injection to improve the antioxidant defenses. The number of renal lesions, plasma glucose and lipid levels, and proteinuria were higher and creatinine clearance was lower in STZ and STZAmlo compared with STZLos and control groups. Glycemia was higher in STZLos compared with control. Blood pressure, basal mitochondrial membrane potential and mitochondrial pyruvate content, and renal oxidized glutathione levels were higher and NADH/cytochrome c oxidoreductase activity was lower in STZ compared with the other groups. In STZ and STZAmlo groups, mitochondrial H2O2 production rate was higher and uncoupling protein-2 content, cytochrome c oxidase activity, and renal glutathione level were lower than in STZLos and control groups. Mitochondrial nitric oxide synthase activity was higher in STZAmlo compared with the other groups. Mitochondrial pyruvate content and H2O2 production rate negatively contributed to electron transfer capacity and positively contributed to renal lesions. Uncoupling protein-2 content negatively contributed to mitochondrial H2O2 production rate and renal lesions. Renal glutathione reduction potential positively contributed to mitochondria electron transfer capacity. In conclusion, AT1 blockade protects kidney mitochondria and kidney structure in streptozotocin-induced diabetes independently of blood pressure and glycemia.