1030-13 Alterations in Endothelial Cell Adenosine Receptors Mediate Endothelium-Dependent Vasoconstriction in Experimental Vein Grafts

Abstract

Adenosine is a potent endogenous vasodilator which mediates its action through A1 and A2 receptor subtypes located on both vascular endothelial and vascular smooth muscle cells (SMC). Adenosine-mediated relaxation in vein grafts has not been examined. This study assesses the in vitro isometric tension responses to specific adenosine receptor agonists (A1: R-phenyl-isopropyl-adenosine and A2: CSG-21680; 10–9 to 10–4 M) of common carotid external jugular vein bypass grafts (VG) in New Zealand White rabbits. These responses were compared to those obtained in the extemal jugular vein (JV) and in the common carotid artery (CA). All vessels were precontracted with prostaglandin F2a (10–5 M). Endothelialized and de-endothelialized vessels were examined. The A1 mediated relaxation in JV was endothelium-independent, whereas A2 mediated relaxation was endothelium-dependent. In CA, A1 mediated relaxation was partially endothelium-dependent, while A2 mediated relaxation was endotheliumindependent. In VG, Al activation induced endothelium-dependent vasoconstriction. Endothelial denudation restored Al mediated relaxation, but reduced compared to that of JV (max. 19 ± 9%). A2 relaxation in VG was endothelium-independent (max. 39 ± 4%). Primary cultures of arterial and vein graft SMC expressed both A1 and A2 receptors on northern blot analysis. There was, however, a marked reduction in the A1 affinity of the SMC from the VG compared to the arterial SMC (40.9 ± 1.3% arterial binding). This study, therefore, demonstrates that there is a substantial change in the adenosine mediated vasoreactivity in VG compared to JV, due to a change in endothelial A1 receptor mediated response from relaxation to constriction, coupled with a decreased affinity of the A1 receptors on the VG SMC. The adenosine responses of the VG are also different from CA. Therefore, the endothelial celis of VG appear to be unique, in that functionally they neither maintain a venous phenotype nor acquire an arterial phenotype in response to adenosine.