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Abstract
Since the sympathetic nervous system has been shown to exert a trophic influence on
vascular smooth muscle cells (SMC), we studied the growth regulating effects of neuropeptide
Y (NPY) in cooperation with the sympathetic co-transmitters noradrenaline and adenosine
triphosphate (ATP) in human vascular SMC. NPY stimulated DNA synthesis in human SMC
grown from subcutaneous arteries and veins (diameter: 0.4 mm) measured by [3H]thymidine
incorporation. Also cell number and protein synthesis were stimulated. The effect
was mediated through the Y1-receptor and not Y2 or Y3 since the Y1-selective NPY analogue
Pro34-NPY and peptide YY stimulated mitogenesis in the same magnitude as NPY while
the NPY-fragment NPY13-36 only had minor effects. The effect was blocked by pretreating
the cells with pertussis toxin indicating a Gi/o-coupled effect. The other sympathetic
co-transmitters, noradrenaline and ATP, also stimulated mitogenesis in the human SMC
in a similar magnitude as NPY. When added together NPY and noradrenaline potentiated
each other in the mitogenic response. ATP had mainly additive effects. This is the
first demonstration that NPY, noradrenaline and ATP stimulates growth in human vascular
SMC. This suggests a role of the sympathetic cotransmitters in modulating vascular
tone, but also by inducing hypertrophy/hyperplasia with possible clinical consequences.