Comparison of the Relaxing Effect of Dopamine with that of Adenosine, Isoproterenol and Acetylcholine in Isolated Canine Coronary Arteries

Abstract

Isolated canine coronary arteries were contracted with prostaglandin F₂α and the relaxing effects of dopamine, adenosine, isoproterenol and acetylcholine were compared. Relaxation induced by dopamine in phenoxybenzamine-treated arteries was not significantly influenced by propranolol and atropine in concentrations sufficient to shift dose-response curves of isoproterenol and acetylcholine, respectively, to the right. Dose-response curves of isoproterenol were shifted significantly to the left by 2 x 10^–5 M aminophylline. In contrast, the relaxing effect of adenosine was significantly attenuated by aminophylline (5 × 10^–6–10^–4 M) in a dose-dependent manner. Kinetic analysis showed that aminophylline competitively antagonized the effect of adenosine, and the pA₂ was 5.57. At these concentrations, aminophylline did not alter the relaxing action of dopamine and acetylcholine. It may be concluded that dopamine produces relaxation at a different site and with a different mechanism of action from those of isoproterenol, the effect of the latter being presumably mediated by cellular cyclic AMP, and that dopamine also does not share the site of action with adenosine and acetylcholine. It appears that receptive sites specific for adenosine are present in canine coronary arteries.