Increased alveolar-capillary membrane permeability by monocrotaline

To study the effect of monocrotaline on the pulmonary alveolar-capillary membrane permeability, cardiac catheterization, extravascular lung water content and absorption of 14C-compounds from the rat lungs in combination with morphological observations were studied in the early stage of monocrotaline intoxications. Purified monocrotaline or its pyrrole was administered to rats with various doses. Single dose of 50 mg/kg of monocrotaline was enough to induce pulmonary hypertension 4 weeks later, but neither immediate nor direct pressor effect was observed by monocrotaline or active pyrrole. Only 3 to 5 mg/kg of pyrrole was enough to produce alveolar flooding with increased extravascular lung water content and accelerated absorption of 14C-mannitol and 14C-inulin from lungs 24 hours after administration. In contrast with fast and potent effect of pyrrole, effect of monocrotaline was mild and delayed in development. These findings suggested that monocrotaline increased the porosity of not only endothelial but also alveolar membrane by active metabolite.