The possibility of development of tolerance of treatment with vasodilators was investigated in 16 patients with severe chronic congestive cardiac failure. Independent of the primary site of action, the first application of a vasodilator resulted in lowering of pulmonary artery pressure by about 30% (isosorbide dinitrate 40 mg orally in delay-action form and 5 mg sublingually, prazosin 2 mg, dihydralazine 75 mg). Only dihydralazine reduced systemic resistance acutely by 42% and increased cardiac minute volume by 66%. After treatment for 12 days with isosorbide dinitrate delay-action (three times 20 mg), prazosin (three times 2 mg) or dihydralazine (three times 75 mg), there was persistent lowering of the pulmonary artery pressure 16 hours after cessation of treatment only after isosorbide dinitrate (-29%) and dihydralazine (-27%). A decrease of systemic resistance by 11% and an increase of cardiac minute volume by 20% were seen only after dihydralazine. An additional acute application of isosorbide dinitrate or dihydralazine resulted in a further decrease of pulmonary artery pressure (-25% and -11%, respectively). An additional decrease of systemic resistance (-23%) and increase of cardiac minute volume (+18%) were again only seen with dihydralazine. In contrast to the first medication there was no significant change of the pulmonary artery pressure after treatment with prazosin for 12 days.

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