COMPARISON OF THE MITOGENIC ACTIVITY OF ANGIOTENSIN-II AND SEROTONIN ON PORCINE ARTERIAL SMOOTH-MUSCLE CELLS

We have investigated the growth promoting activities of two potent vasoactive substances, serotonin and angiotensin II (AII), on cultured porcine aortic smooth muscle cells (ASMC), using a defined serum-free medium. Serotonin (30 nM to 30-mu-M) stimulated ASMC DNA synthesis both alone and in combination with platelet-derived growth factor (PDGF) and epidermal growth factor (EGF). Serotonin-induced DNA synthesis was significantly inhibited by ketanserin (5-hydroxytryptamine-2 (5HT-2) receptor antagonist), but not by LM21009 (5HT-1B receptor antagonist) or by MDL72222 (5HT-3 receptor antagonist). AII (3-100 nM) failed to stimulate ASMC DNA synthesis directly, either alone or in combination with PDGF or EGF. Since both serotonin and All were found to activate phosphatidylinositol turnover and are reported to mobilise intracellular calcium, it is apparent that these events alone are insufficient to stimulate ASMC mitogenesis.