Functional characterization of alpha1-adrenergic receptors in experimental vein grafts.
BACKGROUND: Studies on the pharmacology of the smooth muscle cells in vein bypass grafts suggest that the function of G-proteins and adrenergic receptors is altered. This study examines the alpha-adrenergic responsiveness of smooth muscle cells in vein bypass grafts as compared with those in the common carotid arteries and external jugular veins. METHODS: New Zealand White rabbits received jugular vein interposition bypass grafts of the common carotid. Vessel segments of the vein bypass grafts harvested after 28 days, common carotid arteries, and external jugular veins were sectioned into 5-mm rings (four per vessel) for studies of isometric tension in response to phenylephrine (10(-10) to 10(-4) M) alone and in the presence of prazosin, an alpha1-adrenergic antagonist; WB4101 and 5-methylurapidil (5-MU), alpha1A antagonists; chloroethylclonidine (CEC); an alpha1B antagonist; or the Gi/o G-protein inhibitor pertussis toxin (PTx). RESULTS: All vessels had prazosin-sensitive responses. The jugular veins appear to have functional alpha1A receptors (WB4101 and 5-MU sensitive, CEC insensitive) which are associated with pertussis toxin-sensitive G-proteins. Carotid arteries appear to have atypical alpha1 receptors (WB4101 and 5-MU insensitive, CEC insensitive) associated with pertussis toxin-insensitive G-proteins. Vein grafts appear to have functional alpha1B receptors (WB4101 and 5-MU insensitive, CEC sensitive) which are associated with pertussis toxin-insensitive G-proteins. CONCLUSIONS: These results show that placement of a vein into the arterial circulation induces a change in alpha1-adrenergic receptor subtypes (alpha1A to alpha1B) and in the G-protein coupling of the receptors (PTx sensitive to PTx insensitive), reflecting a signficant phenotypic change in smooth muscle cell signal transduction.
Davies, MG; Huynh, TT; Hagen, PO
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