Adenosine responses in experimental vein bypass grafts

Purpose: Veins develop unique endothelial and smooth muscle cell physiologic phenotypes after implantation as vein grafts in the arterial circulation. Receptor-mediated relaxation is reduced or absent in these grafts. This study examines the responses of vein grafts to adenosine, a known potent endogenous vasodilator, and compares these responses with the native veins and arteries. Methods: The presence of adenosine receptors (A₁ and A₂) by radioligand binding and the in vitro responses to the adenosine analogue N-ethyl-carboxyamido-adenosine were assessed in precontracted common carotid jugular vein bypass grafts placed in New Zealand white rabbits for 28 days. Results were compared with those obtained in precontracted jugular veins and carotid arteries. Both endothelialized and de-endothelialized vessels were studied. The contribution of nitric oxide (NO) and prostanoid production to relaxation was also determined by preincubation with the specific inhibitors L-monomethylarginine and indomethacin, respectively. Finally, the in vitro relaxation in response to the respective A₁ and A₂ adenosine receptor agonists R-phenyl-isopropyladenosine and CGS-21680 was also examined. Results: The results show that the adenosine-induced responses of the vein grafts differ from those of the jugular vein and carotid artery. First, in contrast to the carotid artery, vein graft adenosine-mediated relaxation is NO and prostanoid dependent, similar to the response of the jugular vein. Second, A₁ receptor activation in the vein graft produces an endothelium-dependent contractile response. Third, the A₂ receptor-mediated responses in the vein grafts appear to be independent of the endothelium. Fourth, radioligand studies show the presence of both receptor subtypes (A₁ and A₂) on the vein grafts with a ratio (A₁/A₂ = 1,4) closer to that of the jugular vein (A₁/A₂ = 1.8) than to that seen in the carotid artery (A₁/A₂ = 0.5). Conclusions: Vein graft adenosine responses appear to be unique in that they neither maintain a venous phenotype nor acquire an arterial phenotype. In particular, endothelial A₁ receptor-mediated responses change from relaxation to contraction, and receptor activated NO- mediated relaxation is preserved within the vein grafts probably via A₂ receptor signalling.