Adrenoceptor-mediated modulation of endothelial-dependent vascular smooth muscle growth.
1. Signals derived from endothelial cells (EC) and the sympathetic nervous system are known to independently modulate the growth of vascular smooth muscle (VSM). It is not known if and how these signals are integrated. The purpose of the present study was to test the hypothesis that activation of adrenoceptors 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. Activation of beta-adrenoceptors inhibited this stimulation. EC stimulation of VSM growth was 225+/-31% in the absence and 127+/-27% in the presence of 10 microM 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 directly inhibiting VSM growth. 4. Isoprenaline did not affect EC production of growth factors, as media conditioned 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/VSM 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 sympathetic nervous system and EC coordinately regulate VSM growth.
Damon
D H
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Department of Pharmacology, University of Vermont, Burlington 05405, USA.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D015152:Blotting, Northern; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000187:drug effects*; D024510:Muscle Development; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000254:growth & development*; D011941:Receptors, Adrenergic / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D011941:Receptors, Adrenergic; D016212:Transforming Growth Factor beta