Critical role of the β isoform of protein kinase C (PKCβ) in angiotensin II-induced oxidative stress in vascular smooth muscle cells.

The aim of this study was to elucidate the role of protein kinase Cβ (PKCβ) in subacute angiotensin II (Ang II)-induced oxidative stress and the mechanism of its effects on vascular smooth muscle cells (VSMCs) using a PKCβ-knockout strategy. Both short-term (30 min) and prolonged (24 h) treatment with Ang II increased reactive oxygen species (ROS) production through NADPH oxidase (NOX) activation, with increased phosphorylation of PKCβ at active site Ser660 in rat primary VSMCs from mesenteric artery. The increases in ROS production and NOX activity were completely abolished in VSMCs of PKCβ-knockout rats, in which the absence of PKCβ mRNA expression was confirmed. Genomic and pharmacologic analyses indicated that prolonged treatment with Ang II increased ROS production via NF-κB-mediated NOX1 and p22(phox) expression via the PKCβ/ROS pathway. In vivo infusion of Ang II at a low dose (10 ng/kg/min) for 7 days increased ROS production and NOX1 and p22(phox) expression in mesenteric artery in both male and female non-transgenic rats, and these effects were abolished by PKCβ gene deletion. These results suggest that the PKCβ isoform is the primary regulator of oxidative stress in VSMCs in response to both acute and subacute exposure to Ang II.