The role of the endothelium in mediating the actions of ATP, adenosine and acetylcholine on flow through blood vessels in the rabbit knee joint.

1. An in vitro preparation of the rabbit knee joint, perfused with oxygenated Locke solution, was used to investigate the presence of purinoceptors and the role of endothelium within articular blood vessels. 2. The basal tone of the blood vessels was not affected by adenosine or acetylcholine. Adenosine 5'-triphosphate (ATP) injection produced vasoconstriction which was unaffected by removal of the endothelial layer, but diminished by alpha, beta methylene ATP, a compound which desensitizes P2-purinoceptors. 3. When knee joint blood vessel tone was raised by perfusion with vasopressin (10(-8) M) or 5-hydroxytryptamine (10(-5) M), acetylcholine, ATP and adenosine were all found to induce concentration-dependent relaxation of these vessels. ATP was found to have a dual effect of transient constriction followed by longer-lasting dilatation. 4. 3-Methylxanthine, a P1-purinoceptor antagonist significantly reduced the relaxation response to adenosine but had no effect on the vasodilator effect of ATP. 5. Removal of the endothelial layer virtually abolished the vasodilator effects of acetylcholine and ATP but not adenosine. 6. These results demonstrate that articular blood vessels supplying the rabbit knee contain P1-purinoceptors located on the vascular smooth muscle which mediate vasodilatation. P2-purinoceptors mediating a constrictor effect are also present on this smooth muscle. It is likely that the vasodilator effect of ATP is mediated via P2-purinoceptors located on the endothelial layer.