Different alpha-adrenoceptors mediate migration of vascular smooth muscle cells and adventitial fibroblasts in vitro.
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. Norepinephrine caused dose-dependent migration of both cell types that was dependent on chemotaxis. In contrast, platelet-derived growth factor (PDGF)-BB, used as a positive control, stimulated both chemotaxis and chemokinesis. Only alpha(1D)-adrenoceptors (AR) and alpha(2)-AR antagonists inhibited norepinephrine migration of SMCs, whereas norepinephrine migration of AFBs was only inhibited by alpha(1A)-AR and alpha(1B)-AR antagonists; beta-AR blockade was without effect. Norepinephrine and PDGF-BB were additive for AFB, but not SMC, migration. Stimulation of migration was reversed at high norepinephrine concentrations (10 microM); this inhibition was mediated by alpha(2)- and beta-ARs in AFBs but not in SMCs. Thus norepinephrine induces migration of SMCs and AFBs via different alpha-ARs. This action may participate in wall remodeling and norepinephrine potentiation of injury-induced intimal lesion growth.
Zhang
Hua
H
Department of Cell and Molecular Physiology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Facemire
Carie S
CS
Banes
Albert J
AJ
Faber
James E
JE
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic; D000077214:Becaplermin; D002465:Cell Movement / Q000187:drug effects; D002633:Chemotaxis; D005347:Fibroblasts / Q000166:cytology*; D019329:Idazoxan / Q000031:analogs & derivatives / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology
D000317:Adrenergic alpha-Antagonists; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011942:Receptors, Adrenergic, alpha; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D011943:Receptors, Adrenergic, beta; D000077214:Becaplermin; C058525:2-methoxyidazoxan; D009638:Norepinephrine; D019329:Idazoxan