Fibrotic disorders are typified by excessive connective tissue and extracellular 
matrix (ECM) deposition that precludes normal healing processes in different 
tissues. Angiotensin-II (Ang-II) is involved in the fibrotic response. Several 
muscular dystrophies are characterized by extensive fibrosis. However, the exact 
role of Ang-II in skeletal muscle fibrosis is unknown. Here we show that 
myoblasts responded to Ang-II by increasing protein levels of connective tissue 
growth factor (CTGF/CCN2), collagen-III and fibronectin. These Ang-II-induced 
pro-fibrotic effects were mediated by AT-1 receptors. Remarkably, Ang-II induced 
reactive oxygen species (ROS) via a NAD(P)H oxidase-dependent mechanism, as 
shown by inhibition of ROS production via the NAD(P)H oxidase inhibitors 
diphenylene iodonium (DPI) and apocynin. This increase in ROS is critical for 
Ang-II-induced fibrotic effects, as indicated by the decrease in Ang-II-induced 
CTGF and fibronectin levels by DPI and apocynin. We also show that 
Ang-II-induced ROS production and fibrosis require PKC activity as indicated by 
the generic PKC inhibitor chelerythrine. These results strongly suggest that the 
fibrotic response induced by Ang-II is mediated by AT-1 receptor and requires 
NAD(P)H-induced ROS in skeletal muscle cells.