Spiperone-induced endothelium-dependent relaxation of porcine coronary artery: an investigation into the underlying mechanism.
In pig coronary artery rings contracted by the thromboxane analogue U 46619 (9,11-dideoxy-11 alpha, 9 alpha-epoxy-methano-prostaglandin F 2 alpha), spiperone induced a relaxation which, at 30 mumol/l, corresponded to a complete reversal of the U 46619-induced contraction. The concentration-response curve for spiperone was bell-shaped. The second phase, i.e. the reduction of the relaxant effect (at concentrations above 30 mumol/l) was due to a contractile effect which was the only response in (1) endothelium-denuded arteries, (2) arteries treated with gossypol or methylene blue, or (3) arteries not precontracted with U 46619. Suramin and reactive blue 2 antagonized the relaxing effect, whereas metitepine, spiroxatrine, propranolol, idazoxan, flupenthixol, atropine and 8-phenyltheophylline did not. The endothelium-independent contraction was not reduced by metitepine. In strips of arteries with intact endothelium, incubated with [3H]adenosine and subsequently superfused with physiological salt solution containing dipyridamole, spiperone evoked an increase in tritium overflow above basal efflux. The present results are compatible with the hypothesis that spiperone releases ATP from the pig coronary artery. ATP, in turn, seems to activate endothelial P2 purinoceptors, leading to the release of endothelium-derived relaxing factor (NO) with a subsequent vascular relaxation.