Differential effects of nitroglycerin, trimetazidine, verapamil and SK&F 24260 on venous return as revealed by the open-loop method in the dog.

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Abstract
To obtain detailed information concerning the effects of different vasodilators on venous return, experiments were carried out on 28 dogs by the use of the open-loop method. Blood from the superior and inferior venae cavae was drained at the level of the tricuspid valve into a reservoir, from which blood was pumped into the right atrium at a constant flow rate. Changes in reservoir volume reflected a total blood shift from the experimental dog and indicated changes in venous return. Drugs were administered into the ascending aorta. Nitroglycerin (1-10 μg/kg) decreased systemic blood pressure, total peripheral resistance and venous return but scarcely altered heart rate. Trimetazidine (0.3-3 mg/kg) decreased systemic blood pressure, total peripheral resistance, venous return and heart rate. Verapamil (10-100 μg/kg) decreased systemic blood pressure, total peripheral resistance and heart rate, and increased venous return. SK&F 24260 (1-10 μg/kg) decreased systemic blood pressure, total peripheral resistance and increased venous return. Only high doses (10-30 μg/kg) of SK&F 24260 reduced heart rate. Rigorous measurements of systemic output showed that nitroglycerin (10 μg/kg), trimetazidine (3 mg/kg), verapamil (100 μg/kg), SK&F 24260 (10 μg/kg) produced no change in this parameter. SK&F 24260 increased venous return even when sino-aortic baroreceptor reflex was eliminated, ruling out reflex venoconstriction as a possible cause of the increased venous return. The results suggest the following: [1] Vasodilators like SK&F 24260 and verapamil increase venous return by decreasing arterial and/or venous resistance. [2] If the effect which increases venous capacitance prevails over the effect which decreases arterial and/or venous resistance, venous return is reduced as is the case of nitroglycerin and trimetazidine.