Alteration of monocrotaline pyrrole-induced cardiopulmonary effects in rats by hydrallazine, dexamethasone or sulphinpyrazone.

The effects of intraperitoneal hydrallazine, dexamethasone, or sulphinpyrazone on the toxicity of monocrotaline pyrrole (MCTP) were examined in rats 14 days after injection of MCTP (5 mg kg-1, i.v.). MCTP alone caused increases in lung weight, and of both lactate dehydrogenase activity and protein concentration in bronchopulmonary lavage fluid. Right ventricular hypertrophy also occurred. Hydrallazine (3 mg kg-1, daily), a vasodilator and platelet prostaglandin synthesis inhibitor, reduced the degree of right ventricular hypertrophy and the elevation in the concentration of protein in lavage fluid. Dexamethasone (27 micrograms kg-1, daily), an anti-inflammatory agent and inhibitor of phospholipase, also reduced the right ventricular hypertrophy and the increased protein concentration in lavage fluid caused by MCTP. Sulphinpyrazone (100 mg kg-1, twice daily), an inhibitor of platelet prostaglandin biosynthesis, prevented right ventricular hypertrophy in the MCTP treated rats without affecting any of the indices of lung injury. These results provide further support for the hypothesis that platelets and vasoconstrictor agents play a role in the development of MCTP-induced pulmonary hypertension.