Effect of alpha-methyldopa on lung microembolism in the rat

The effect of chronic pretreatment with alpha-methyldopa on acute pulmonary hypertension induced by lung microembolization with Sephadex particles in the rat was studied. Alpha-methyldopa was administered twice a day for 10 days by oesophageal gavage (20 mg X kg-1 of body weight) prior to embolization. Rats were anaesthetized with urethane. A catheter was positioned in closed chest rats in the pulmonary artery and 50 microliter of Sephadex suspension in saline were injected. The control group was not pretreated with alpha-methyldopa. In a subgroup of control and pretreated rats, the cardiac output was measured by the dye dilution technique before and after lung microembolization. Rats pretreated with alpha-methyldopa had less pulmonary hypertension, higher cardiac output and more severe arterial hypoxaemia 15 min after lung microembolization than untreated animals. There was no difference in platelet counts prior and after embolization. We suggest that pulmonary hypertension after lung microembolization in the rat includes a vasoconstrictor component which can be suppressed by alpha-methyldopa, and that severe arterial hypoxaemia in pretreated rats is probably the result of a decrease of the ventilation/perfusion ratio in unobstructed areas, which in untreated rats may be prevented by active vasoconstriction.