Purine-mediated relaxation and constriction of isolated rabbit mesenteric artery are not endothelium-dependent

The distribution of P₁- and P₂-purinoceptors in isolated transverse ring preparations of rabbit mesenteric artery was studied by comparing responses to ATP, α, β-methylene ATP and adenosine in the presence and absence of endothelium. At resting tone in the presence of endothelium, ATP, α, β-methylene ATP and acetylcholine, but not adenosine, produced transient concentration-dependent contractions. α, β-Methylene ATP was 5000 times more potent than ATP in this respect. Contractions to ATP or α, β-methylene ATP in intact preparations were not significantly different from preparations without endothelium, but contractions to acetylcholine were significantly enhanced in the absence of endothelium. In the presence of endothelium, after desensitisation of the preparations to α, β-methylene ATP, contractions to ATP, but not those to noradrenaline, were either greatly reduced or abolished. In preparations with tone raised by noradrenaline, acetylcholine, ATP and adenosine each produced relaxation in the presence of endothelium; however, in the absence of the endothelium, relaxations to acetylcholine were abolished, while those to ATP and adenosine were not significantly altered. 8-Phenyltheophylline significantly antagonised relaxation to adenosine in the presence of endothelium, whereas relaxation to ATP was unaffected. In raised tone preparations, with and without endothelium, α, β-methylene ATP caused further contraction. However, in raised tone preparations with or without endothelium, that had been desensitised to α, β-methylene ATP before elevation of muscle tone, ATP still caused relaxation, whereas α, β-methylene ATP had no effect. These results indicate that in the rabbit mesenteric artery, ATP acts at purinoceptors located on smooth muscle, but not on endothelium, to produce both contraction and relaxation, possibly via two subclasses of the P₂-purinoceptor, and that adenosine acts at P₁-purinoceptors located on smooth muscle to produce relaxation.