Bradykinin receptor modulation in vein grafts

Following vein grafting, bradykinin B2 receptor-mediated responses in the vein graft are decreased and B1 receptor-mediated responses are increased. It is not known whether these changes in bradykinin receptor responses are due to nonspecific changes, local inflammation, or arterial hemodynamics. Four experimental tissue models were studied to discriminate among these possibilities. Twelve New Zealand white rabbits underwent excision of native vein (n = 4), external jugular veno-venous bypass (n = 4), or common carotid veno-arterial bypass (n = 4). Grafts and unoperated contralateral jugular veins (n = 4) were harvested at 28 days postoperatively. Isometric tension studies were performed on four rings from each vein and vein graft. The responses to bradykinin, a B2 agonist (BK; 10^-17 to 10^-5 M) and des-Arg⁹-bradykinin, a B1 agonist (DABK; 10^-17 to 10^-5 M) were recorded. Compared to native veins, the results show a progressive attenuation in BK sensitivity in contralateral veins, veno-venous grafts, and veno-arterial grafts, and the development of DABK sensitivity in the contralateral veins and both vein graft models. The alterations in B2 receptor-mediated responses appear therefore to be induced by a combination of the surgical procedure and arterialization, while changes in B1 receptor-mediated responses appear to be related solely to nonspecific sensitization of the cardiovascular tissue following the operative procedure. Thus, it appears from this study that there are two distinct mechanisms involved in the modulation of bradykinin receptors in vein grafts after implantation into the arterial circulation.