VSM growth is stimulated in sympathetic neuron/VSM cocultures: role of TGF-beta 2 and endothelin

Sympathetic nerves are purported to stimulate blood vessel growth. The mech anism(s) underlying this stimulation has not been determined. With use of a n in vitro coculture model, the present study tests the hypothesis that sym pathetic neurons stimulate the growth of vascular smooth muscle (VSM) and e valuates potential mechanisms mediating this stimulation. Sympathetic neuro ns isolated from superior cervical ganglia (SCG) stimulated the growth of V SM. Growth of VSM in the presence of SCG (856 +/- 81%) was significantly gr eater 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 SC G 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 pla y a role in the physiological and/or pathological growth of the vasculature .