Introduction. Angiotensin II (AngII) regulates blood pressure and water and electrolyte metabolism through the stimulation of NAD(P)H oxidase and production of reactive oxygen species (ROS) such as O 2 -, which is metabolised by superoxide dismutase, catalase and glutathione peroxidase. We assessed the role of AT 1 and AT 2 receptors, NAD(P)H oxidase and protein kinase C (PKC) in Ang II-induced sodium and water excretion and their capacity to stimulate antioxidant enzymes in the rat hypothalamus, a brain structure known to express a high density of AngII receptors. Materials and methods. Male Sprague-Dawley rats were intracerebroventricularly (ICV) injected with AngII and urinary sodium and water excretion was assessed. Urine sodium concentration was determined using flame photometry. After decapitation the hypothalamus was microdissected under stereomicroscopic control. Superoxide dismutase, catalase and glutathione peroxidase activity were determined spectrophotometrically and extracellular signal-regulated kinase (ERK1/2) activation was analysed by Western blot. Results. AngII-ICV resulted in antidiuresis and natriuresis. ICV administration of losartan, PD123319, apocynin and chelerythrine blunted natriuresis. In hypothalamus, AngII increased catalase, superoxide dismutase and glutation peroxidase activity and ERK1/2 phosphorylation. These actions were prevented by losartan, apocynin and chelerythrine, and increased by PD123319. Conclusions. AT 1 and AT 2 receptors, NAD(P)H oxidase and PKC pathway are involved in the regulation of hydromineral metabolism and antioxidant enzyme activity induced by AngII.
La nefropatía es una de las complicaciones más importantes de la diabetes, la cual puede conducir a la muerte. Las kinasas activadas por mitógenos (MAPK) son conocidos mediadores del daño renal en la diabetes, cuya activación (fosforilación) se encuentra asociada al aumento de la síntesis de proteínas de la matriz extracelular (colágeno, fibronectina, entre otras) y a la fibrosis renal. Recientemente, se ha establecido a la planta Ruellia tuberosa L. como antioxidante, antiinflamatoria, antidiabética y nefroprotectora en varios modelos experimentales. En este trabajo se evaluó el efecto del tratamiento con 10 mg/kg/día, p.o, del extracto acuoso de la raíz de R. tuberosa (RT) durante cuatro semanas, sobre la fosforilación de la ERK 1/2 en la corteza renal de ratas control y con diabetes tipo I inducida por la estreptozotocina y se vinculó con los marcadores de la fibrosis renal tales como el aumento del peso del riñón, contenido de proteínas totales y de colágeno I. Los resultados demuestran que el tratamiento con RT previno el aumento de la fosforilación de las ERK 1/2, del peso del riñón, y del contenido de proteínas y de colágeno I renal por en la diabetes inducida por ETZ. Los hallazgos contribuyen a la elucidación de los mecanismos por los cuales R. tuberosa protege al riñón frente a la diabetes, estableciéndose así la actividad antifibrótica de esta especie utilizada en la medicina popular venezolana.
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