Proliferative effects of angiotensin II and endothelin-1 on guinea pig gingival fibroblast cells in culture

• Published in: Comparative biochemistry and physiology. Toxicology & pharmacology 2002-08, Vol.132 (4), p.451-460
• Main Authors: Ohuchi, Nozomi, Koike, Katsuo, Sano, Masakazu, Kusama, Tadashi, Kizawa, Yasuo, Hayashi, Kazuhiko, Taniguchi, Yumiko, Ohsawa, Masami, Iwamoto, Keishi, Murakami, Hajime
• Format: Article
• Language: English
• Subjects: Angiotensin II; Angiotensin II - metabolism; Angiotensin II - pharmacology; Animals; AT 1 receptor; Captopril; Cells, Cultured; Endothelin-1; Endothelin-1 - metabolism; Endothelin-1 - pharmacology; ET A receptor; Fibroblasts - cytology; Fibroblasts - drug effects; Fibroblasts - metabolism; Gingiva - cytology; Gingiva - drug effects; Gingiva - metabolism; Gingival fibroblast; Guinea Pigs; Male; Nifedipine; Phenytoin; Proliferation
• ISSN: 1532-0456; 1878-1659
• DOI: 10.1016/S1532-0456(02)00098-4

We investigated whether phenytoin (PHT) and nifedipine (NIF) induce angiotensin II (Ang II) and endothelin-1 (ET-1) generation by cultured gingival fibroblasts derived from guinea pigs and whether Ang II and ET-1 induce proliferation of these cells. Immunohistochemical experiments showed that PHT (250 nM) and NIF (250 nM) increased the immunostaining intensities of immunoreactive Ang II and ET-1 (IRET-1) in these cells. Captopril (3 μM), an angiotensin-converting enzyme inhibitor, reduced these enhanced intensities to control levels. Ang II (100 nM) enhanced the immunostaining intensity of IRET-1. PHT (250 nM) and NIF (250 nM)-induced cell proliferation. Both PHT- and NIF-induced proliferation was inhibited by captopril (3 μM). Ang II (100 nM) and ET-1 (100 nM) also induced cell proliferation. Ang II-induced proliferation was inhibited by CV11974 (1 μM), an AT 1 receptor antagonist and saralasin (1 μM), an AT 1/AT 2 receptor antagonist, but not by PD123,319 (1 μM), an AT 2 receptor antagonist. ET-1-induced proliferation was inhibited by BQ123 (10 μM), an ET A receptor antagonist, but not by BQ788 (1 μM), an ET B receptor antagonist. These findings suggest that PHT- and NIF-induced gingival fibroblast proliferation is mediated indirectly through the induction of Ang II and ET-1 and probably mediated through AT 1 and ET A receptors present in or on gingival fibroblasts.