Coronary responses to dilating substances and competitive inhibition by theophylline in the isolated perfused guinea pig heart.

Abstract

Coronary dilation induced by infusion of adenosine, adenine nucleotides, dipyridamole, and papaverine was quantitated in the spontaneously beating isolated perfused guinea pig heart. Theophylline antagonized the effects of all the substances tested. The inhibition proved to be reversible and of a competititve type. Single injections of ADP and ATP induced flow increases which were more rapid in onset and of greater magnitude than those due to equimolar amounts of adenosine. Lowering the perfusate temperature prolonged coronary responses to ADP and ATP more than those to adenosine. Papaverine produced greater maximal dilation than adenosine. Theophylline inhibited papaverine-induced dilation less effectively than dilating responses to adenosine and other compounds. In the potassium arrested heart, the dilation caused by compound D 600 and papaverine was sensitive to the perfusate calcium concentration but that due to adenosine was unaffected. Dipyridamole, which was equipotent to adenosine in the non-arrested hear, became less potent than adenosine in the arrested heart. The results favour the view that all of the substances tested induce coronary dilation per se and that their effects are not mediated by adenosine. The dilator response to papaverine is assumed to be the result of two effects, one of which is inhibited by theophylline, the other by high extracellular calcium.