ALPHA(2)-ADRENERGIC RECEPTORS INCREASE CELL-MIGRATION AND DECREASE F-ACTIN LABELING IN RAT AORTIC SMOOTH-MUSCLE CELLS

Vascular wound healing and such pathologies as atherosclerosis and res tenosis are characterized by migration and proliferation of the smooth muscle cells of the media after denudation of the intima. To explore possible roles that alpha(2)-adrenergic receptors (alpha(2)-ARs) might have in these cellular responses, we characterized the alpha(2)-ARs p resent in explant-derived cultures of rat aortic smooth muscle (RASM) cells. The results of immunofluorescence microscopy and reverse transc ription followed by the polymerase chain reaction indicated that all t hree alpha(2)-AR subtypes (alpha(2A), alpha(2B), and alpha(2C)) were i nitially present. Mitogen-activated protein kinase activity in the RAS M cells was stimulated fivefold over basal by the alpha(2)-selective a gonist dexmedetomidine (Dex) and was blocked by coincubation with the alpha(2)-selective antagonist rauwolscine (RW) or by preincubation of the cells with the G(i)/G(o)-protein inhibitor pertussis toxin. alpha( 2)-AR activation by Dex did not promote cell proliferation, as measure d by the incorporation of [H-3]thymidine. However, Dex significantly i ncreased RASM cell migration, and antagonist blocked this effect. Incu bation of RASM cells with Dex also produced a marked decrease in F-act in labeling, which again was prevented by coincubation with RW. The ev idence clearly reveals the presence of functional alpha(2)-ARs in RASM cells. The involvement of alpha(2)-AR activation with cytoskeletal ch anges and cell migration is novel and indicates a potential role of th ese receptors in vascular wound healing and pathogenesis.