1029-16 The Function of G-Proteins and Alpha-Adrenergic Receptors in Retrieved Human Vein Grafts

Abstract

Although little is known about the pharmacology of the smooth muscle cells of human saphenous vein coronary artery bypass grafts, there is evidence to suggest that the function of G-proteins and alpha-adrenergic receptors is altered. This study examines the alpha-adrenergic function of smooth muscle cells of aorto-coronary vein bypass grafts and saphenous veins obtained from eight patients undergoing repeat coronary artery bypass grafting for recurrent ischemic symptoms. After removal from the patient, each specimen was placed into oxygenated Krebs solution, rapidly cleaned, dissected and patent segments sectioned into 5 mm rings (4 per vessel) for isometric tension studies to phenylephrine (10 -10 to 10 -4 M) alone and in the presence of the alpha-adrenergic 1A antagonist WB4101, the 1B antagonist chloroethylclonidine, and the G-protein inhibitor, pertussis toxin. The results suggest that the saphenous veins have a homogenous population of alpha adrenergic population (1B) which are coupled to pertussis toxin insensitive G-proteins (Table). The retrieved vein grafts show a predominantly homogenous alpha adrenergic population (1A). which are coupled to pertussis toxin sensitive G-proteins (Table). Saphenous Vein Vein Graft Phenylephrine (control) 5.04 ± 0.09 5.79 ± 0.16 * WB4101 (10 -5 M) 5.16 ± 0.33 4.73 ± 0.18 † Chloroethylclonidine (0 -5 M) 4.74 ± 0.15 # 5.38 ± 0.23 Pertussis Toxin (100 μ g/ml) 4.87 ± 0.28 4.87 ± 0.16 Mean ± s.e.m., –log 10 [EC 50 ] * p < 0.05 compared to saphenous vein # p < 0.05 † P < 0.01 compared to phenylephrine control These results show changes both in receptor sub-type and functional coupling to G-proteins, associated with arterio-venous grafting, possibly reflecting changes in smooth muscle cell phenotype.