Induction of B-1-kinin receptors in vascular smooth muscle cells: Cellularmechanisms of MAP kinase activation

Vascular smooth muscle cell (VSMC proliferation is a prominent feature of t he atherosclerotic process that occurs after endothelial injury. Although a vascular wall kallikrein-kinin system has been described, its contribution to vascular disease remains undefined. Because the BI-kinin receptor subty pe (B1KR) is induced in VSMCs only in response to injury, we hypothesize th at this receptor may be mediating critical events in the progression of vas cular disease. In the present study, we provide evidence that des-Arg(9)-br adykinin (dABK) (10 (-8) M), acting through B1KR, stimulates the phosphoryl ation of mitogen-activated protein kinase (MAPK) (p42(mapk) and p44(mapk)). Activation of MAPK by dABK is mediated via a cholera toxin-sensitive pathw ay and appears to involve protein kinase C, Src kinase, and MAPK kinase. Th ese findings demonstrate that the activation of B1KR in VSMCs leads to the generation of second messengers that converge to activate MAPK and provide a rationale to investigate the mitogenic actions of dABK in vascular injury .