Involvement of reactive oxygen species in the activation of tyrosine kinase and extracellular signal-regulated kinase by angiotensin II

Reactive oxygen species (ROS) have been proposed to mediate vascular hypert rophy induced by angiotensin II (Ang II). Recently, we and others have show n that growth-promoting signals by Ang II involve protein tyrosine kinase ( PTK) and extracellular signal-regulated kinase (ERK). However, whether ROS contribute to the Ang II-induced PTK and/or ERK activation in vascular smoo th muscle cells (VSMCs) remains largely unclear. Here, we have investigated the possible involvement of ROS in Ang II-induced PTK and ERK activation. In the presence of a NADH/NADPH oxidase inhibitor, diphenyleneiodonium (DPI ) or an antioxidant, alpha-tocopherol, Ang II-induced protein tyrosine phos phorylation of two major proteins (p120, p70) and ERK activation were marke dly reduced, whereas ERK activation by epidermal growth factor was unaffect ed. DPI also inhibited Ang II-induced H2O2 production and PTK activation. I n this regard, H2O2 and a membrane permeable thiol-oxidizing agent, diamide , stimulated protein tyrosine phosphorylation of p120 and p70, and ERK acti vation in VSMCs. H2O2 also enhanced PTK activity. From these data, we concl ude that ROS play a critical role in the Ang II-induced PTK and ERR activat ion in VSMCs, thereby contributing to vascular growth associated with enhan ced Ang II activity.