Rat aortic smooth-muscle cell proliferation is bidirectionally regulated in a cell cycle-dependent manner via...

In the cardiovascular system, vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) have been well characterized as potent vasodepressors or vasodilators. However, their pathophysiological implication in proliferation of vascular smooth muscle cells has not yet been elucidated. In the present study, we have first identified PACAP/VIP type 2 receptor as a dominant type in rat vascular smooth muscle cell (VSMC) by RT-PCR. PACAP and VIP increased cyclic AMP accumulation with similar potency. In 24-h [3H]thymidine incorporation assay, PACAP or VIP exhibited a suppressive effect on the DNA synthesis of rat VSMC stimulated by serum when added at the late G1 phase. In contrast, when added at G0/G1 phase of the cell cycle, PACAP or VIP enhanced the serum-induced DNA synthesis. In 24-h incubation, PACAP alone has little mitogenic activity. However, when incubated up to 48 h, PACAP stimulated significantly the DNA synthesis and the cell proliferation of rat VSMC. These results suggest that PACAP and VIP regulate the proliferation of rat VSMC by enhancing or suppressing in a cell cycle-dependent manner and induce delayed mitogenesis and cell proliferation.