Crotalaria-induced pulmonary hypertension. Uptake of 3H-thymidine by the cells of the pulmonary circulation and alveolar walls.

Feeding with Crotalaria spectabilis seeds induces 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 has been assessed at two levels of the pulmonary artery--the hilum and the periphery. In the hilar pulmonary artery, a biphasic increase in labeling index (LI) is seen in each cell type. After 3 days of feeding, the medial smooth muscle cells show a slight but significant increase (1.5 times the control value), and, after 7 days, so do the adventitial fibroblasts (3 x) and the endothelial cells (EC) (2 x). After 14 days LI for all three cell types is again at control values, but after 21 days (wall thickness is no increased) each cell type shows at least a fivefold increase; by 35 days all are again near control levels. In the intra-acinar region, by 14 days, "newly" muscularized arteries are identified and increase in number and proportion up to 35 days; 3H-thymidine uptake is not evident in this cell type until 35 days have passed. The ECs of these arteries, however, show a striking increase in LI after 14 days as do those of the alveolar capillaries. The ECs of the intra-acinar veins show a biphasic response being increased after 7, 28, and 35 days. The present study has shown that Crotalaria ingestion induces hyperplasia and hypertrophy of pulmonary arterial cells at pre- and intra-acinar levels. The early increase in LI probably represents a response to the original cell injury, the later changes, a response to continuing damage or, in part, adaptation to the pulmonary hypertension now present.