Influence (Gingival Hyperplasia) of Nifedipine in Oral Region

1993 Fiscal Year Final Research Report Summary

• Project/Area Number: 04671133
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: 畜産化学
• Research Institution: Nihon University
• Principal Investigator: FUJII Akira Nihon Univ.Sch, Dent.Matsudo, Assoc.Prof., 松戸歯学部, 助教授 (70102564)
• Co-Investigator(Kenkyū-buntansha): 山根 潤一 日本大学, 松戸歯学部, 講師(専任扱) (20220428) ; 中尾 寿美 日本大学, 松戸歯学部, 助手 (20102577) ; MATSUMOTO Hiroko Nihon Univ.Sch, Dent.Matsudo, Instructor, 松戸歯学部, 副手 (50221594) ; AKIMOTO Yoshiaki Nihon Univ.Sch, Dent.Matsudo, Assist.Prof., 松戸歯学部, 専任講師 (10147720) ; YAMAMOTO Hirotugu Nihon Univ.Sch, Dent.Matsudo, Prof. (00102591)
• Project Period (FY): 1992 – 1993
• Keywords: Gingival hyperplasia / Nifedipine / Gingival fibroblasts / Tissue culture / Intracellular calcium resoinse / Bradykinin / 細胞増殖 / DNA合成能

Research Abstract

It has been reported that phenytoin, cyclosporin A, and calcium channel blockers caused gingival hyperplasia. Especially, a number of studies has been reported on phenytoin. The interesting point is that all of these compounds possess somewhat calcium blockin effect, but no report exists on the study between calcium blocking effect and gingival hyperplasia. In recent years, calcium channel blockers have been used extensively for the treatment of disease in cardiovascular system, accompanied with gingival hyperplasia as their untoward effects. Among of the calcium channel blockers, nifedipine caused it most frequently with appearance rate of 6 to 30%. The common histopathological observations are increased number of fibroblasts, increased fibrous connective tissue (collagen fiber). inflammatory changes (such as cell infiltration and dilatation of capillaries), and irregular elongation of rate pegs. In order to clarify the mechanism of gingival hyperplasia by nifedipine, the present inve stigation was undertaken to study the effect of calcium channel blockers ongingival fibroblasts derived from nifedipine responder (nifediline reactive patients ; NIFr) and non-responder (nifedipinenon-reactive patients ; NIFn) by comparing these two cell lines.
The results show that NIFr gave higher cell proliferation rate, DNA synthesis, and collagen synhesis in the presence of calcium channel blockers. One of the important factor for the initiation of cell proliferation or cell differenciation is the transient and rapid change of intracellular calcium. Thus, the effect of chemical mediators was investigated on intracellular calcium ([Ca^<2+>]i) response, because inflammation was accompanied with gingival hyperplasia in most of the cases. As the result, [Ca^2]i response was greatly affected by bradykinin, thrombin, PGE_28 PGF_<2alpha>, and PDGF in gingival fibroblasts derived fron NIF_n, whereas by histamine and bombesin in ones derived from NIFr. Thus, histamine might play more important role in gingival hyperplasia. Bradykinin gave the greatest effect on [Ca^<2+>]i response in both gingival fibroblasts derived from NIFn. The [Ca^<2+>]i response by bradykinin was temperature dependent and the highest response was obtained at 37ﾟC.This response was inhibited by bradykinin B_2 antagonist.