IQUIMEFA   05518
INSTITUTO QUIMICA Y METABOLISMO DEL FARMACO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Participation of the endoplasmic reticulum stress in the adrenal medulla of DOCA-salt hypertensive rats. Implication of the endothelins
Autor/es:
MERCEDES SCHOLLER; JUAN C. PERAZZO; MARIA JULIA GUIL; LILIANA G. BIANCIOTTI; LUIS CASSINOTTI; MARCELO S. VATTA
Lugar:
Praga
Reunión:
Congreso; The Fifteenth International Conference on Endothelin; 2017
Resumen:
Increasing evidence supports the role of the endoplasmic reticulum (ER) stress, a response to unfolded or misfolded protein accumulation, in the pathogenesis of diverse diseases including cardiovascular pathologies. Given that endothelins (ETs) are intimately involved in development and/or maintenance of hypertension, we aimed to evaluate the relationship of ETs and the ER stress in the adrenal medulla of DOCA-salt rats. Sulfisoxazole, a mixed ETA/ETB antagonist was orally administered to control and hypertensive rats. Following euthanasia adrenal medulla were harvested for western blot analysis and transmission electronic microscopy (TEM) studies. Systolic blood pressure, heart rate and the components of the unfolded protein response (UPR) pathway were increased in hypertensive rats. Furthermore, adrenal medulla cells showed ER swelling as well as gap junction disruption, inter e intra-edema, nuclear interdigitation and necrotic areas as revealed by TEM. Animals treated with sulfisoxazole showed significantly reduced blood pressure, heart rate, UPR components and ultraestructural damage including ER swelling. These findings support that blockade of ET receptors reduces ER stress and cell damage in the adrenal medulla of DOCA-salt hypertensive rats along with an improvement of the hemodynamic parameters.