Amrinone dilates pulmonary vessels and blunts hypoxic vasoconstriction in isolated rat lungs

The direct effects of the cardiotonic agent amrinone (WIN 40680) on pulmonary vasoreactivity were studied in isolated, blood-perfused, rat lungs. Lungs were perfused at constant flow and ventilated with normoxic gas, while mean pulmonary arterial pressure was monitored. Pressor responses to hypoxic gas (3% O2, 5% CO2) and angiotensin II (0.25 microgram/0.1 ml) were elicited after amrinone or saline was added to the perfusate. Pressor responses were blunted when calculated amrinone perfusate concentration was increased to 10 micrograms/ml. Pressor responses to hypoxia fell from 8 +/- 1 mm Hg (mean +/- SE, n = 8) before, to 2 +/- 1 mm Hg after amrinone (10 micrograms/ml), while responses to angiotensin II fell from 7 +/- 1 to 3 +/- 1 mm Hg (n = 8). Pressor responses in saline controls did not change. Pulmonary arterial pressure dropped within minutes following injection of amrinone (300 micrograms) into the pulmonary arterial cannula, with a greater drop during hypoxia than during normoxia. Meclofenamate did not prevent blunting of pressor responses by amrinone. Amrinone is a rapidly acting vasodilator which blunts vasoconstriction due to hypoxia or angiotensin II. Since it combines cardiotonic and pulmonary vasodilator actions, amrinone may have therapeutic potential for patients with cor pulmonale and pulmonary hypertension.