EFFECTS OF GENISTEIN AND STAUROSPORINE ON ANGIOTENSIN-II-INDUCED DNA-SYNTHESIS, PROTEIN-SYNTHESIS AND MITOGEN-ACTIVATED PROTEIN-KINASE ACTIVATION IN VASCULAR SMOOTH-MUSCLE CELLS

This study examines the effects of protein kinase inhibitors and activ ator on angiotensin II-induced DNA synthesis and protein synthesis of rat aortic smooth muscle cells. In quiescent confluent cells, angioten sin II induced a concentration-dependent increase in thymidine incorpo ration and leucine incorporation. The tyrosine kinase inhibitor genist ein caused an inhibition of the angiotensin II-induced DNA synthesis b ut not of the agent-induced protein synthesis. The protein kinase C in hibitors staurosporine and calphostin C caused an inhibition of the an giotensin II-induced protein synthesis but not of the agent-induced DN A synthesis. The protein kinase C activator phorbol 12-myristate 13-ac etate stimulated protein synthesis. Angiotensin II stimulated mitogen- activated protein (MAP) kinases and the angiotensin II-induced MAP kin ase activation was inhibited by genistein but not by staurosporine. Th ese findings suggest that angiotensin II-induced DNA synthesis is at l east partly mediated via protein-tyrosine phosphorylation and angioten sin II-induced protein synthesis is at least partly mediated by activa tion of protein kinase C. It seems likely that MAP kinase activation i s involved in DNA synthesis but not in protein synthesis induced by an giotensin II.