Characterization of dopamine-mediated relaxation in experimental vein bypass grafts

Background. Dopamine is an endogenous inotropic agent commonly used during coronary artery surgery and in the medical therapy of a revascularized pati ent. In this study the responses of intimal hyperplastic vein grafts to dop amine are examined. Methods. The in vitro isometric tension responses to dopamine of common car otid jugular vein bypass grafts in New Zealand White rabbits were determine d, The responses were compared to those obtained in the jugular vein and in the common carotid artery, Both endothelialized and denuded vessels were p recontracted with prostaglandin F-2 alpha and the responses to dopamine wer e assessed. The contributions of nitric oxide and prostanoids to the respon se were also determined. Results. Each vessel showed a biphasic dose response to dopamine with relax ation at low concentrations followed by contraction at high concentrations, Dopamine relaxation in the jugular vein was endothelial independent while in the carotid artery it was endothelial dependent and decreased, The sensi tivity of both vessels was significantly greater than the vein graft (6.62 +/- 0.12; P < 0.05); however, after endothelial denudation, the sensitivity of dopamine-mediated relaxation of the vein graft (8.91 +/- 0.09) was sign ificantly enhanced. Preincubation with L-NMMA (to block NO synthesis) inhib ited vein graft relaxation to dopamine and preincubation with indomethacin (to block cyclooxygenase activity) inhibited carotid artery relaxation to d opamine, Addition of phenoxybenzamine, a broad alpha-adrenergic antagonist, enhanced dopamine relaxation in the jugular vein and depressed the relaxat ion in the carotid artery, There was no effect on the dopamine response in the vein graft, Jugular vein and carotid artery responded to dopamine with cholera toxin-sensitive (G alpha(s)) responses. In contrast, dopamine relax ation in the vein graft was enhanced by inhibition of G alpha(s). Conclusion. Dopamine relaxation in vein grafts is mediated in part by NO bu t not by either prostanoids or a-adrenergic receptor activation, It is dimi nished compared to native vessels due to an endothelium-dependent, G alpha( s)-mediated pathway, (C) 2000 Academic Press.