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Articles in PresS, published online ahead of print January 10, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00858.2001
Submitted on October 2, 2001
Accepted on January 8, 2002
-Adrenoceptors Mediate Migration of Vascular Smooth Muscle Cells and Adventitial Fibroblasts In Vitro
1 Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
2 Orthopaedics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
* To whom correspondence should be addressed. E-mail: jefaber{at}med.unc.edu.
Norepinephrine directly induces growth of the vascular wall, which may involve not only proliferation of smooth muscle cells (SMCs) and adventitial fibroblasts (AFBs) but also augmentation of their migration. To test this hypothesis, growth-arrested SMCs and AFBs from rat aorta were exposed to norepinephrine (NE). NE caused dose-dependent migration of both cell types that was dependent on chemotaxis. In contrast, PDGF-BB, used as a positive control, stimulated both chemotaxis and chemokinesis. Only 1D-AR and 2-AR antagonists inhibited NE migration of SMCs, whereas NE migration of AFBs was only inhibited by 1A-AR and 1B-AR antagonists; ß-AR blockade was without effect. NE and PDGF-BB were not additive or synergistic toward each other for SMC migration, but were thus for AFB migration. Stimulation of migration was reversed at high NE concentrations (10 µmol/L); this inhibition was mediated by 2- and ß-ARs in AFBs but not in SMCs. Thus, NE induces migration of SMCs and AFBs via different -ARs. This action may participate in wall remodeling and NE potentiation of injury-induced intimal lesion growth.
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