Oxidative Stress in Multiple Organ Damage in Hypertension, Diabetes and CKD, Mechanisms and New Therapeutic Possibilities

Hypertension, diabetes, hypercholesterolemia and chronic kidney disease (CKD) lead to cardiovascular (CV) events and cardiovascular death consists of main cause in mortality of those diseases. Understanding of pathophysiology that links them and CV events has been vigorously studied and several factors are believed to play roles such as NO, reninangiotensin system, and oxidative stress. It has been shown that those factors affect endothelial function and consequently organ circulation as well as function and viability of cells and organs. Despite overwhelming evidences in the consequences of experimental models of ROS-induced organ damage, large-scale clinical trials of former antioxidant therapies, such as vitamin C, vitamin E or -carotene, could not demonstrate satisfactory benefit to patients and they seemed to be harmful in some cases (Hennekens et al., 1996; Omenn et al., 1996; Virtamo et al., 1998; Hercberg et al., 1999; Lee et al., 1999; Yusuf et al., 2000; de Gaetano, 2001; Heart, 2002; Vivekananthan et al., 2003; Hercberg et al., 2004; KrisEtherton et al., 2004; Lonn et al., 2005). Several studies concluded that β-carotene supplementation increased the relative risk of death in patients with some types of cancer and had no benefit on patients with cardiovascular disease. Another study said vitamin E increased hemorrhagic stroke. Even antioxidant cocktails increased in all-cause motality (Omenn et al., 1996; Rosen et al., 2001a). So far, supplementation with vitamins C and E, either alone or in combination with each other or with other antioxidant vitamins, does not appear to be efficacious for the treatment of cardiovascular disease (Lonn et al., 2005). We investigated role of oxidative stress in consequences of multiple organ damages in mouse and possible new therapeutic agent.