Endothelium-dependent relaxations to adenosine in juvenile rabbit pulmonary arteries and veins

We studied the actions of adenosine and its analogues 5'-(N- ethylcarboxamido)-adenosine (NECA) and N⁶-cyclohexyladenosine (CHA) in pulmonary vessels isolated from juvenile rabbits. Pulmonary arteries relaxed in a concentration-dependent fashion to all three compounds. Pretreatment with the methylxanthine 8-p-sulfophenyltheophylline shifted the concentration-response curves to adenosine and NECA rightward, indicating that the vasodilator effects were mediated by the adenosine receptor. The order of potency of adenosine compounds was NECA > adenosine > CHA, indicating that the A₂-receptor mediates relaxations to adenosine in rabbit pulmonary arteries. Endothelium rubbing attenuated relaxations to adenosine at concentrations of ≤3 x 10^-7 M and to all NECA concentrations. Inhibition of nitric oxide synthase with N(G)-nitro-L-arginine (L-NNA) similarly attenuated relaxations at concentrations of ≤3 x 10^-7 M for adenosine and ≤3 x 10^-8 M for NECA. With the use of the same methods, a substantial endothelial contribution was additionally observed in pulmonary veins to the vasodilator effects of NECA. We conclude that adenosine, and the more specific A₂-receptor agonist NECA, dilate pulmonary arteries and veins isolated from young rabbits via a mechanism that is partially dependent on endothelium-derived nitric oxide.