Adrenoceptor-mediated modulation of endothelial-dependent vascular smooth muscle growth

1 Signals derived from endothelial cells (EC) and the sympathetic nervous s ystem are known to independently modulate the growth of vascular smooth mus cle (VSM). It is not known if and how these signals are integrated. The pur pose of the present study was to test the hypothesis that activation of adr enoceptors by sympathetic-derived catecholamines modulates EC regulation of VSM growth. 2 The effects of adrenergic agonists on VSM growth were studied in vitro in EC/VSM cocultures. EC stimulated VSM growth in EC/VSM cocultures. Activati on of beta -adrenoceptors inhibited this stimulation. EC stimulation of VSM growth was 225 +/- 31% in the absence and 127 +/- 27% in the presence of 1 0 muM isoprenaline. Activation of alpha -adrenoceptors had no effect on EC stimulation of VSM growth in coculture. 3 Isoprenaline did not affect the growth of VSM grown in the absence of EC, suggesting that it did not inhibit EC stimulation of VSM growth by directl y inhibiting VSM growth. 4 Isoprenaline did not affect EC production of growth factors, as media con ditioned by EC grown in the absence or presence of isoprenaline, stimulated VSM growth to the same extent. Isoprenaline did not alter EC, VSM or EC/VS M production of the VSM growth inhibitor transforming growth factor beta -1 (TGF-beta1). 5 These data provide evidence that catecholamines, via activation of beta - adrenoceptors, can modulate EC-dependent VSM growth, and suggest that the s ympathetic nervous system and EC coordinately regulate VSM growth.