Drug discovery for improvement of chronic kidney disease and cardiovascular disease

Abstract

Chronic kidney disease (CKD) has been increasingly recognized as a major public health problem in the world. Recent studies have showed that CKD is an independent risk factor for the occurrence of cardiovascular disease (CVD). Reactive oxygen species (ROS), generated by reduction-oxidation actions, have been generated by reduction-oxidation actions, recognized as the important chemical mediators that regulate signal transduction in various cells including vascular smooth muscle cells (VSMC) and mesangial cells (MC). It has been showed that increase in ROS generation may relate to a risk for CVD and CKD. In addition, ROS mediate activation of mitogen-activated protein (MAP) kinases, extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase, p38, and big MAP kinase 1, in various cells leading to change in gene expressions. Control of the oxidative stress and ROS-mediated alterations of signaling molecules including MAP kinases may provide new therapeutic strategy against CKD and CVD. In this review, we summarize mainly our data regarding the pharmacological effects of renin-angiotensin-aldosterone system blockers, bioflavonoids and adiponectin in VSMC and MC. Also we review the data on a possible new class drug against oxidative stress to improve CKD and CVD. © The Pharmaceutical Society of Japan.