High salt diet increases glomerular ROS formation through an ET-1/ETA dependent mechanism (1134.9)

Endothelin-1 (ET-1) stimulates the production of reactive oxygen species (ROS) in pulmonary artery smooth muscle cells and also activates NADPH oxidase in isolated aortic rings. The connection between ROS production provides mechanistic insight into possible deleterious effects of ET-1 dysregulation during pathological processes such as hypoxia. ET-1 production is increased by a high salt diet (HSD), so we sought to test the effects of HSD on the capacity of glomeruli to produce ROS. C57BL6/J mice were placed on a normal or HSD and then treated with or without selective ETA antagonist ABT-627 for one week (5 mg/kg/d p.o.). Untreated animals on a HSD had significantly increased levels of glomerular ROS production when stimulated by phorbol (PMA) mediated PKC activation compared to glomeruli from normal salt controls (77.5±7.8 v. 23.7±7.3 thousand ALU/mg protein, p<0.01, n=5-6). However, HSD animals treated with ABT-627 had a blunted increase in glomerular ROS production (44.3±11.5 thousand ALU/mg protein, ...