VSM growth is stimulated in sympathetic neuron/VSM cocultures:: role of TGF-β2 and endothelin

Sympathetic nerves are purported to stimulate blood vessel growth. The mechanism(s) underlying this stimulation has not been determined. With use of an in vitro coculture model, the present study tests the hypothesis that sympathetic neurons stimulate the growth of vascular smooth muscle (VSM) and evaluates potential mechanisms mediating this stimulation. Sympathetic neurons isolated from superior cervical ganglia (SCG) stimulated the growth of VSM. Growth of VSM in the presence of SCG (856 +/- 81%) was significantly greater than that in the absence of SCG (626 +/- 66%, P < 0.05). SCG did not stimulate VSM growth in transwell cocultures. An antibody that neutralized the activity of transforming growth factor-beta 2 (TGF-beta 2) inhibited SCG stimulation of VSM growth in coculture. SCG stimulation of VSM growth was also inhibited by an endothelin A receptor antagonist. These data suggest novel mechanisms for sympathetic modulation of vascular growth that may play a role in the physiological and/or pathological growth of the vasculature.