Athymic nude rats develop severe pulmonary hypertension following monocrotaline administration

Objective: To investigate the significance of the presence or absence of th e thymus in the development of pulmonary hypertension (PH) following monocr otaline (MCT) administration, the degree of MCT-induced PH (MCT-PH) in athy mic nude (F344/N Jcl-rnu) rats was compared with that in their euthymic (rn u/+) littermates. Methods: Histopathological studies of the lung in terms o f interstitial edema, congestion, thickening of the alveolar wall, inflamma tory cell infiltration and degeneration of arteries were performed by stain ing with hematoxylin-eosin (HE), elastin van Gieson and Masson's trichrome. The medial wall thickness of the small pulmonary arteries and the weight r atio of the right ventricular free wall (RV) to that of the left ventricle plus septum [RV/(LV + S) weight ratio] were used as indices of the degree o f PH. Toluidine blue staining was performed to estimate the number of the m ast cells in the lung interstitium. Results: Interstitial edema was signifi cantly severer in MCT-injected euthymic rats than in MCT-injected athymic n ude rats (p < 0.01); in contrast, the thickening of the alveolar wall was s everer in MCT-injected athymic nude rats than in MCT-injected euthymic rats (p < 0.05). The degree of MCT-PH, as determined by the medial wall thickne ss of the small pulmonary arteries and RV/( LV + S) weight ratio in MCT-inj ected athymic nude rats, was significantly severer than in MCT-injected eut hymic rats (p < 0.05 and p < 0.01, respectively). The number of mast cells was significantly greater in MCT-injected athymic nude rats than in MCT-inj ected euthymic rats (p < 0.01). The degree of the medial wall thickness of the small pulmonary arteries was significantly correlated with RV/(LV + S) weight ratio (p < 0.05) as well as with the number of mast cells in MCT-inj ected rats. Conclusions: Athymic nude rats developed severer PH than euthym ic rats along with a greater number of mast cells and severer histopatholog ical changes, such as thickening of the alveolar wall. Mast cell proliferat ion was considered to play a pivotal role in the development of PH in MCT-P H. (C) 2000 S. Karger AG, Basel.