Effect of methylprednisolone on monocrotaline-induced pulmonary vascular disease and right ventricular hypertrophy

Methylprednisolone (MP) has been shown to reduce acute lung edema caused by monocrotaline (MCT), but its effect on MCT-induced pulmonary hypertension has not previously been reported. We have examined the effects of MP on MCT-induced pulmonary vascular remodeling and right ventricular hypertrophy using five groups of rats. Group 1 received nothing and acted as control; group 2 and all other groups received MCT as a single injection; group 3 was given low-dose MP by daily injection starting 24 hours after the MCT; group 4 was given MP as two high-dose pulses 2 hours before and 22 hours after MCT; group 5, acting as control for injection, received an injection of water 2 hours before MCT and daily for 21 days. All animals were killed 21 days after the MCT was given; ventricular weights were determined, and the lung vasculature was analyzed morphometrically. In each of the last three groups, the "treatment" reduced the increase in arterial medial thickness, "extension" of muscle to intraacinar pulmonary arteries, number of vessels with "occluded" lumen, and right ventricular hypertrophy--the features caused by MCT alone. For all four features, the effectiveness of a given regimen was similar. Daily MP prevented three-quarters of the ventricular ratio change, whereas pulse MP and daily water prevented one-half. The protection given by daily water injection may relate to autologous hormone production (steroid or other) from stress of injections. Daily MP, given after the acute MCT injury has occurred, protects more effectively than a high-dose pulse given at the time of injury. We suggest that the acute phase of MCT injury causes secondary changes that, although triggered by the acute lesion, become self-sustaining and are more significant for vascular structural remodeling.