Effects in renal and cardiac tissue from CKD rat model: antioxidant evaluation of treatment with the selective endothelin‐receptor antagonist atrasentan and the combination of atrasentan with the vitamin D receptor activator (paricalcitol), and the angiot (404.4)

Abstract

Diabetes is the number one cause of chronic kidney disease (CKD). However, the highest mortality in CKD patients is attributed to cardiovascular disease (CVD) complications. It have been shown that processes producing reactive oxygen species (ROS) in the renal and cardiac tissues are involved in these pathologies. For instance, searching for therapies contributing to decrease ROS, in addition of controlling the CKD and CVD clinical manifestations is highly justified. In this study, we assessed the antioxidant effects of paricalcitol (vitamin D receptor activator) (UP), enalapril (angiotensin converting enzyme inhibitor) (UE), atrasentan (selective endothelin‐receptor antagonist) (UA), and the combination of these (UEAP) in cardiac and renal tissue of 5/6 nephrectomized uremic rat model. The left ventricle (LV) and kidney (KY) tissues were evaluated and compared to a uremic control (UC) and a non‐uremic control (NC). Lipid peroxidation was reduced by UEAP to levels comparable to NC in both tissues. Cardiac glutathione peroxidase activity (GPx) was significantly higher in UP and furthermore in UEAP; while UE showed the higher renal GPx. Glutathione reductase activity (GRx) at the LV was increased by UA and moreover by UE. Renal catalase activity was restored by UA and UEAP to levels comparable to NC, as did UEAP and UE at LV. In LV, UEAP showed Cu/Zn‐SOD and Mn‐SOD activity levels comparable to NC. The UE was the only one showing differences in eNOS and iNOS, confirming previous findings. Our data suggested that UA, and to a greater extent, UEAP provided increased antioxidant activity with potential to improve CDK and CVD clinical manifestations caused by ROS.Grant Funding Source: NIH R25GM096955