Cbymase-dependent angiotensin II (AngII) production plays a role in vascular proliferation，and also in the production of endothelins through chymase cleavage of big endothelin (ET)．We have reported that Ang II and ET-l play a crucial role in the development of gingival fibroblast proliferation induced by drugs such as phenytoin(PHT)，nifphedipine (NIF) and cyclosporineA (CsA). Therefore，in the present experiment，using cultured rat gingival fibroblasts，We investigated whether chymase contributes the promotion of drug-induced gingival proliferation. Immunocytochemistry revealed that fibroblasts treated with PHT，NIF and CsA showed an increase in the intensity of immunostaining for Ang II and ET-1 in comparison with the control，and this imunostaining was reduced to the control level by pretreatment of fibroblasts with chymostatin. Furtbemore，chymase (0.1-0.5 unit/ml) induced concentration-dependent fibroblast prolifbration. The proliferative response to 0.2 unit/ml. Chymase was inhibited by TAK044(ET receptor antagonist). These findings suggest that chymase may contribute to promotion of the proliferative response of gingival fibroblasts to PHT and NIF．
P1J-13-1
