Future directions in vasodilator therapy for heart failure. Vasodilator therapy has become a major pharmacologic approach for improving left ventricular function, and consequently, vasodilator drugs are being used increasingly in the treatment of heart failure. Ideally, vasodilator drugs used in the long-term management of heart failure should show clearly defined pharmacodynamic effects. These include reduced impedance to left ventricular ejection, increased venous capacitance, increased left ventricular ejection fraction and reduced heart size, absence of neurohormonal stimulation, and slowed progression of left ventricular dysfunction. The mechanisms of action and sites of activity of the various vasodilator drugs currently available vary considerably, and none as yet has proved ideal for the treatment of heart failure or hypertension. The complexity surrounding the multiple vasoconstrictor mechanisms involved in heart failure has led to a rationale for combined vasodilator therapy and certain combinations are discussed. From a therapeutic standpoint, the development of drugs with multiple mechanisms of action is particularly attractive. Flosequinan is a new vasodilator agent whose cellular mechanism of action remains uncertain. Flosequinan has the advantage of being able to relax both arterial and venous beds and as such may be particularly beneficial in the treatment of heart failure. 