Angiotensin II-induced ET and PGI(2) release in rat aortic endothelial cells is meditated by PKC

Angiotensin II (Ang II) has been shown to stimulate the release of immunore active endothelin (ET) from cultured bovine ECs. Also, Ang II activates pho spholipase A(2) (PLA(2)) in various tissues, resulting in the release of ar achidonic acid and formation of prostaglandins. We used rat aortic endothel ial cells to investigate the role of protein kinase C (PKC) in Ang II-induc ed release of both ET and prostacyclin (PGI(2)). The amount of ET and PGI(2 ) produced were determined by radioimmunoassay. Ang Ii-induced the release of both ET and PGI(2). Pretreatment with 10(-6)M of any one of the PKC inhi bitors: 1-(5-isoquinolinesulfonyl) piperazine(CL), staurosporine, 1-(5-isoq uinolinesulfonylmethyl)piperazine(H7), and calphostin C blocked AII-induced release of both ET and PGI(2). In rat aortic endothelial cells that were t reated with either AII or PDBu, PKC enzyme assay showed PKC was translocate d from the cytosol to the membrane which indicates activation. This suggest s that PKC mediates All-induced ET and PGI(2) release. In summary, All acti vates PKC which inhibits rat aortic endothelial cells ET and PGI(2) formati on, and this inhibition can be overcome by pretreatment with PKC inhibitors .