Background: Angiotensin II (AngII) increases reactive oxygen species (ROS) and induces glomerular sclerosis. Toll-like receptor 4 (TLR4)-mediated inflammation enhances the renal impairment in renal inflammatory diseases. The relationship between TLR4 and AngII-induced glomerular sclerosis is unknown.Methods: Mice lacking TLR4 function (Tlr4^{lps-d}) and wild-type (WT) mice were randomized into groups treated with AngII, norepinephrine (NE) or a sub-depressor dose of the AngII receptor blocker irbesartan along with AngII for 2 weeks. We then assessed the expressions of NADPH oxidase and monocyte chemoattractant protein-1 (MCP-1) and the inflammatory cell recruitment in the glomeruli. We also evaluated the mesangial matrix proliferation and ROS.Results: AngII and NE equally increased the systolic blood pressure compared to the control mice (p<0.05). In the WT mice treated with AngII, we observed glomerular sclerosis, an increase in NADPH oxidase, MCP-1 and the infiltration of macrophages as well as ROS content in the glomeruli compared to the control mice (p<0.05), whereas the Tlr4^{lps-d} mice showed little effects of AngII on these indices. In addition, the sub-depressor-dose irbesartan treatment reversed these changes. NE had little effects on these indices. Conclusions: TLR4 plays an important role in AngII-induced oxidative stress, inflammation and glomerular sclerosis through the AT1 receptor.

We investigated the relationship between myocardial oxidative stress and cardiac sympathetic hyperactivity in patients with takotsubo cardiomyopathy (TC) compared with acute anteroseptal myocardial infarction (AMI). Methods: In 10 TC patients and 10 AMI patients, electrocardiogram, echocardiography, cardiac catheterization were conducted, and plasma catecholamines and urinary (U) 8-hydroxy-2’-deoxyguanosine (8-OHdG) as a marker of oxidative DNA damage were taken for one week from onset. Results: On admission, the coronary sinus (CS) had significantly higher norepinephrine (NE) and 8-OHdG levels than the aortic root (Ao) and peripheral blood vessels. Circulating catecholamines in TC patients tended to be higher than those in AMI patients