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

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Abstract
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 α, beta methylene ATP, a compound which desensitizes P2-purinoceptors. 3 When knee joint blood vessel tone was raised by perfusion with vasopressin (10−8m) 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.

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