The release of a coronary vasodilator metabolite from the guinea-pig isolated perfused heart stimulated by catecholamines, histamine and electrical pacing and by exposure to anoxia.

1 A procedure involving two guinea-pig isolated hearts perfused in series is described for detecting in the recipient heart the release of a possible coronary vasodilator metabolite from the donor heart. 2 Adrenaline and isoprenaline stimulated the rate and force of contraction and produced a multiphasic coronary vascular response, the predominant phase of which was vasodilatation. When the beta-adrenoceptors of the recipient heart were blocked, stimulation of the donor heart by the catecholamines was associated with a coronary vasodilatation of the recipient heart. 3 Histamine stimulated rate and force of contraction and was predominantly coronary vasodilator. After blockade of histamine H1- and H2-receptors in the recipient heart, coronary vasodilatation followed increases in activity of the donor heart in response to histamine. 4 These vasodilator responses of the recipient heart were attributed to the release from the donor heart of a vasodilator metabolite by the increased activity. This is the proposed mechanism for the predominant coronary vasodilator response to catecholamines and histamine. 5 Periods of electrically-paced tachycardia and anoxia of the donor heart also led to the release of vasodilator activity. 6 The possible identity of the metabolite is discussed.