Actividad de las enzimas antioxidantesen el riñon de la rata con preeclampsia experimental / Rat kidney antioxidant enzyme activities in experimental preeclampsia

La preeclampsia (PE) es un trastorno multisistémico del embarazo caracterizado por hipertensión, proteinuria y edema. La PE se asocia con la disfunción endotelial, el estrés oxidativo y con la disminución de la actividad de la sintasa del óxido nítrico (SON) endotelial. Los mecanismos de la vasodilatación asociada al embarazo normal sugieren que el óxido nítrico (NO) es el más importante mediador en la reducción de la resistencia vascular, mientras que en la PE la respuesta dilatadora dependiente de endotelio y mediada por el NO se encuentra reducida. Se ha demostrado que la inhibición de la síntesis del NO mediante la administración crónica de LNAME en ratas preñadas, resulta en un modelo animal que ocasiona un síndrome similar a la PE, el cual cursa con hipertensión, proteinuria, trombocitopenia y retardo de crecimiento intrauterino. Con el fin de caracterizar las alteraciones renales que ocurren durante la PE, empleamos este modelo animal de preeclampsia inducido por la inhibición de la SON, en ratas de 13 días de gestación. Se cuantifico la posible alteración en la actividad de las enzimas antioxidantes como la catalasa (CAT), superoxido dismutasa (SOD) y glutatión peroxidasa (GPx), así como la SON renal. El tratamiento crónicocon L-NAME en ratas preñadas incrementó la PAM (+20mmHg), produjo proteinuria, sin embargo no altero significativamente el número y el peso de los fetos. El estudio histológico de los riñones de animales pre-eclámpticos mostró que los mismos presentan tumefacción turbia de epitelios tubulares, focos hemorrágicos y congestión de capilares glomerulares. El tratamiento crónico con L-NAME en las ratas preñadas redujo la actividad de las tres enzimas antioxidantes evaluadasy de la SON renal. Estos hallazgos sugieren que la PE experimental cursa con alteración renal asociada con la reducciónde la actividad antioxidante y la inhibición de la SON.

Preeclampsia (PE) is a multisystem disorder of pregnancy characterized by hypertension, proteinuria and edema. PE is associated with endothelial dysfunction, oxidative stress and decreased endothelial nitric oxide synthase activity. The mechanisms of normal pregnancy-associated vasodilation suggest that nitric oxide (NO) is the most important mediator for the reduction of vascular resistance. Many studies demonstrat ereduction of endothelium-dependent dilator response mediated by NO in PE. Inhibition of NO synthesis is an animal model which results in a PE-like syndrome, hypertension, proteinuria, thrombocytopenia and intrauterine growth retardation. In order to assess the possible renal alteration in this animal model of preeclampsia induced by chronic administration of L-NAME, we determined the antioxidant enzymes activities (catalase, superoxide dismutase and gluthation peroxidase) and nitric oxide sinthase in the rat kidney. Chronic L-NAME treatment in pregnant rats increased MAP (+20mm Hg), produced proteinuria and did not change the number and weight of fetuses. Histological examination of the kidneys showed cloudy swelling PE tubular epithelia, hemorrhagic fociand congestion of glomerular capillaries. In addition, L-NAME treatment reduced CAT, SOD, GPx and NOS activity in the kidney. These findings suggest that in experimental preeclampsia, renal alterations are associated with a reduction in the antioxidant enzyme and NOS activities.

Role of endothelin in stress-induced hypertension.

In this study we investigated the role of endogenous endothelin in the cardiovascular response to acute stress, ie mild footshocks in conscious rats. Footshock-stress significantly increased mean arterial pressure and heart rate (P < 0.05). Peripheral or intracerebroventricular (IVT) administration of BQ 788, a selective antagonist of ET(B) receptor, did not alter pressor response to footshocks. Intraperitoneal injections of BQ 123 (1 mg/kg), a selective antagonist of the ET(A)-receptor, had a tendency to decrease, while BQ 123 (203 ng/5 microl) IVT administration significantly reduced the pressor response to footshocks (-12 mm Hg, P < 0.001). Neither ET(A) nor ET(B) antagonists, when injected centrally or peripherally, altered basal blood pressure or heart rate. Our results may indicate a role of brain endothelin in the sympathetic mediated cardiovascular response to stress, via stimulation of ET(A) receptor.

Endothelin ETA receptors subtype mediates phosphoinositide hydrolysis in adrenal medulla.

We investigated the effect of endothelins (ETs) on receptor-mediated phosphoinositide turnover in whole adrenal medulla. Endothelin -1, -2, -3 increased phosphoinositide (PI) turnover by 30% in whole adrenal medulla prelabeled with (3H)myoinositol. ET-stimulation of PI hydrolysis was almost completely dependent on the presence of the extracellular calcium since its chelation resulted in a blockade of ETs induced InsP1 accumulation. Addition of cadmium increased basal and ETs-stimulated InsP1 accumulation. ETs induced InsP1 accumulation was inhibited by BQ 123, a selective antagonist of the ETA receptor, while BQ 788, a selective antagonist of the ETB receptor, was ineffective. The selective agonist at the endothelin ETB receptor, IRL 1620, was ineffective to induce changes in inositide metabolism. Our data indicate that stimulation of PI turnover constitutes one of the signalling pathways of ETs in rat adrenal medulla and that this action is mediated through ETA receptor activation. These results suggest that endothelin could play a role in the regulation of adrenal medulla function.