EFFECTS OF MONOCROTALINE PRETREATMENT OF RATS ON REMOVAL OF 5-HYDROXYTRYPTAMINE AND NORADRENALINE BY PERFUSED LUNG

The alkaloid, monocrotaline, causes significant pulmonary damage in many species, including the rat. We, therefore, determined whether the inactivation of biogenic amines by perfused lungs of rats was modified by prior treatment of the animals with monocrotaline. Young rats (45 to 50 g) treated for 21 days with monocrotaline (22 μg/ml) in their drinking water developed right ventricular hypertrophy. Treated animals gained weight more slowly and consumed less food and water than control rats that drank tap water. Lungs from monocrotaline‐treated animals were heavier and had a higher protein content than control lungs. Isolated lungs from treated animals removed and metabolized 50% less perfused 5‐hydroxytryptamine than did controls. The diminished 5‐hydroxytryptamine metabolism was probably due to impaired delivery of substrate to intrapulmonary monoamine oxidase (MAO) since MAO activity in 600 g supernatant fractions of homogenates of lungs from monocrotaline‐treated rats was not different from control values. Pulmonary removal of perfused noradrenaline was decreased about 60% by the 21‐day treatment, suggesting that the effects of monocrotaline were somewhat nonspecific. These effects were not caused by monocrotaline directly, since perfusion of lungs from untreated animals with this drug did not alter removal of co‐perfused 5‐hydroxytryptamine. Reduced pulmonary removal of circulating biogenic amines following pretreatment with monocrotaline may reflect damage to capillary endothelium, which could also affect other metabolic functions of lung. 1978 British Pharmacological Society