CROTALARIA-INDUCED PULMONARY-HYPERTENSION - UPTAKE OF THYMIDINE-H-3 BY THE CELLS OF THE PULMONARY CIRCULATION AND ALVEOLAR WALLS

Abstract

Feeding with C. spectabilis seeds induced the following structural changes in the pulmonary arterial circulation characteristic of pulmonary hypertension: increased medial and adventitial thickness, the appearance of muscle in smaller arteries than normal and reduction in the number of peripheral arteries. By autoradiographic techniques, after injection of 3H-thymidine into rats fed Crotalaria for 3, 7, 14, 21, 28 or 35 days, the contribution of hyperplasia to these changes was assessed at 2 levels of the pulmonary artery, the hilum and the periphery. In the hilar pulmonary artery, a biphasic increase in labeling index (LI) was seen in each cell type. After 3 days of feeding, the medial smooth muscle cells showed a slight but significant increase (1.5 times the control value) and after 7 days, so did the adventitial fibroblasts (3 times) and the endothelial cells (EC) (2 times). After 14 days, LI for all 3 cell types was at control values but after 21 days (wall thickness increased) each cell type showed at least a 5-fold increase; by 35 days all were near control levels. In the intraacinar region, by 14 days, newly muscularized arteries were identified and increased in number and proportion up to 35 days; 3H-thymidine uptake was not evident in this cell type until 35 days had passed. The EC of these arteries showed a striking increase in LI after 14 days as did those of the alveolar capillaries. The EC of the intraacinar veins showed a biphasic response which increased after 7, 28 and 35 days. The present study showed that Crotalaria ingestion induced hyperplasia and hypertrophy of pulmonary arterial cells at pre- and intraacinar levels. The early increase in LI probably represented a response to the original cell injury, the later changes, a response to continuing damage or in part, adaptation to the pulmonary hypertension present.