Angiotensin not only raises blood pressure and modifies body fluids and electrolytes but also induces differentiation and proliferation of fibroblasts in the circulatory system in order to repair damage. The purpose of the present study was to observe the influence of the addition of angiotensin II (AngII) or nifedipine (NIF) alone or both sequentially on proliferative activity, the intracellular Ca(2+) concentration ([Ca(2+)]i), and the inositol-1,4,5-triphosphate (IP3) level in cultivated human gingival fibroblasts. Addition of 10(-8)-10(-4) M NIF or 10(-5)-10(-4) M AngII alone increased the proliferation of cultivated gingival fibroblasts, and the interaction of NIF and AngII suppressed proliferation. Addition of AngII alone increased [Ca(2+)]i, with a peak 60 s afterward and a return to a level slightly higher than the pretreatment level at 120 s. Addition of both AngII and NIF did not increase [Ca(2+)]i as much as the addition of AngII alone. When Ca(2+) was absent from the extracellular environment, the AngII-induced increase in [Ca(2+)]i was suppressed. AngII increased the concentration of IP(3), with a peak at 120 s after its addition. From these results we concluded that AngII increased the proliferation of gingival fibroblasts by causing an influx of Ca(2+), which increased [Ca(2+)]i.
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