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

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Abstract
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. 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 β‐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. 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. 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. Periods of electrically‐paced tachycardia and anoxia of the donor heart also led to the release of vasodilator activity. The possible identity of the metabolite is discussed.