Abstract
Administration of monocrotaline in rats causes hypertensive changes in the pulmonary vasculature, focal pneumonitis and mast cell hyperplasia in the lung. In order to investigate the role of mast cell hyperplasia in monocrotaline-induced pulmonary changes, changes of mast cell density and histamine content in rat lung were studied after monocrotaline administration (40mg/kg, s. c.) with or without ketotifen treatment (2mg/kg, every 8 hours). After monocrotaline administration, mast cell density in lung tissue decreased at 1wk (0.67±0.41/mm2), but increased by 4wk (307.4±152.6/mm2) 136 times control value (2.25±1.5/mm2). Histamine content in lung tissue (control: 0.6±0.23mcg/g wet weight) increased as much as 144-fold in 4 weeks (86.7±50.5mcg/g).
There was significant correlation between the degree of right ventricular hypertrophy (RV/LV+S) to histamine content in lung tissue and to mast cell density in relation to the various types of treatment. Ketotifen treatment did not prevent the development of pulmonary hypertension which was evaluated by the elevation of right ventricular systolic pressure in right heart catheterization, but significantly reduced right ventricular hypertrophy. Ketotifen treatment did not significantly inhibit the increase of mast cell density and serum histamine content, but decreased the histamine content in lung tissue significantly by 4wk. Because of the anti-histamine activity of ketotifen, the present data revealed that histamine contained in mast cell has no pathogenetic role in the development of monocrotaline-induced pulmonary hypertension. We consider that pronounced mast cell hyperplasia probably reflects the existence of hyperplastic stimulation for lung cells which was typically shown as pneumonitis.
