Proposed mechanism of Cdc42GAP regulation in smooth muscle cells. Contractile activation may activate NAD(P)H oxidases, which consist of the membrane associated catalytic complex including gp91phox homologue (NOX1 or NOX4) and p22phox, and cytoplasmic regulatory subunits containing p47phox, p67phox, p40phox and Rac. Activated NAD(P)H oxidases in turn stimulate the generation of ROS in cells. Increased ROS may suppress the activity of Cdc42GAP, which leads to Cdc42 activation and facilitate smooth muscle contraction via the PAK1/vimentin pathway. Cdc42 activity may also be regulated by GEFs.