Abstract-The question of whether the coronary blood vessels contain an intrinsic adrenergic mechanism for vasodilatation of physiological significance has been ex amined in the canine heart-lung preparation with a donor by studying the response of the coronary vessels to epinephrine, norepinephrine, isoproterenol and salbutamol in combination with practolol. To differentiate the vasodilatation mediated through adrenoceptors in the coronary vessels from that resulting from an increase in the myo cardial 02 consumption, a special method of analysis was developed based on the linear relation between the coronary flow and the myocardial 02 consumption.It was found that all four compounds produced an increase in the coronary flow attri butable to an increased myocardial 02 consumption.Epinephrine and norepinephrine produced a decrease in the coronary flow after practolol which completely abolished the increase in the myocardial 02 consumption as well as the positive inotropic and chrono tropic effects produced by these compounds, while isoproterenol and salbutamol pro duced an increase. These results indicate that adrenergic-receptor exists in the coronary subserving a vasodilatation.However, the vasodilatation through this mechanism is of minor importance under physiological conditions and becomes com pletely masked in the presence of an overwhelmingly strong vasodilatation consequent to an increase in the myocardial 02 consumption. as manifested by relaxation in isolated coronary artery strips (1) and in the non-beating heart (2) do not necessarily mean that ;3-adrenergic receptor activity in the coronary vessels plays a paramount role in the coronary vasodilatation of the intact beating heart, since cate cholarnines produce in vivo a marked change in the mechanical and metabolic activities of the myocardium, which can, in its turn, affect the tone of the coronary vessels consider ably.

Using the canine heart-lung preparation supported by a donor dog and the isolated right and left atrial preparations of the guinea-pig and the rat, the cardiac actions of dibutyryl cyclic AMP were studied and compared with those of cyclic. AMP. Dibutyryl cyclic AMP produced positive isotropic and chronotropic effects associated "ith an increase in the coronary flow, while cyclic AMP produced negative isotropic and chronotropic effects, together with an increase in the coronary flow. Propranolol did not alter the effects of dibutyryl cyclic AMP. The negative isotropic and chronotropic effect of cyclic AMP was antagonized by aminophylline, while the positive isotropic and chronotropic effect of dibutyryl cyclic AMP vvas potentiated by this compound.Whereas the coronary flow increase by dibutyryl cyclic AMP seas associated with an increase in the myocardial oxygen consumption, there was no increase in the myocardial oxygen consumption after cyclic AMP. It is concluded that dibutyryl cyclic AMP passed the surface membrane and exerted its effect after having been converted to cyclic AMP within the cell. Cyclic AMP was presumed to remain outside the cell and produce its effect in the same way as adenine nucleotides and adenosine produce their effect.The positive isotropic effects of catecholamines have been postulated to result from an increase in the intracellular level of cyclic AMP produced by activation of adenyl cvclase. This hypothesis is based on the following observations: (a) myocardial adenyl cvclase in broken cell preparations is activated by catecholamines ~ 1 ): .b,, tissue level of cyclic AMP in the intact heart muscle increases in response to catecholamine stimulation 2 5 and (c 1 the isotropic response to catecholamines is enhanced by theophylline (6'1, which has been shown to inhibit phospho-diesterase, the enzyme responsible for metabolic degradation of cyclic AMP to 5'-AMP. One observation at variance with the above hypothesis has been the failure to reproduce the inotropic effects of catecholamines by administration of exogenous cyclic AMP (2, 6 -8). Levine and Vogel (9) reported that the injection of large doses of cyclic AMP in unanesthetized humans and dogs resulted in a prompt increase in heart rate and cardiac output, but the possibility that the observed changes could have been reflexly induced cannot be ruled out. However, it has been shown that cyclic AMP does not pass the cell membrane at a rate sufficient to achieve an effective intracellular concentration ;2;, a finding which may explain the inability of cyclic AMP to alter myocardial contractility. To facilitate passage across cellular mem branes, a derivative of cyclic AMP, N6-2'-O-dibutyryl-cyclic 3', 5'-AMP (dibutyryl cyclic

Using the canine heart-lung preparation supported by a donor, the effects of ethyl adenosine-5'-carboxylate (EAC) on the heart and coronary circulation were studied and compared with those of adenosine. EAC produced qualitatively similar effects to adenosine in this preparation. Aminophylline inhibited the effects of EAC as well as those of adenosine. Dipyridamole did not potentiate the effects of EAC, while it produced a definite potentiation of the effects of adenosine.

No abstract

Abstract-To indentify the histamine-receptors in the canine myocardium, experiments were performed in the canine heart-lung preparation supported by a donor.