α₂-Adrenergic receptors stimulate cell migration and decrease cytoskeletal organization in rat aortic smooth muscle cells

Vascular wound healing and pathology is characterized by migration and proliferation of medial smooth muscle cells following denudation of the intima. To explore potential physiological roles that α₂-adrenergic receptors (α₂-ARs) may play in smooth muscle, the presence of the three subtypes as well as the functions they mediate, were examined. Immunofluorescent microscopy, revealed the presence of all three subtypes in explant-derived cultures of rat aortic smooth muscle (RASM) cells. The expression of all three subtypes was verified using RT-PCR. Stimulation of α₂-ARs with the selective agonist dexmedetomidine (Dex) lead to a 5-fold increase in MAP kinase activity. This was blocked in the presence of the antagonist rauwolscine (RW) as well as by treatment with pertussis toxin. Interestingly, treatment of RASM cells with Dex stimulated cell migration which could be blocked by co-incubation with RW. Dex, however, did not stimulate cell proliferation as measured by [³H]thymidine incorporation. Incubation of RASM cells with Dex also produced a marked decrease in f-actin labeling, which again, was prevented by co-incubation with RW. The evidence reveals the presence of functional α₂-ARs in RASM cells. The involvement of α₂-ARs with cell migration and cytoskeletal changes is novel and indicates a potential role in vascular wound healing or pathogenesis.