ENDOTHELIN-1 CAUSES SEQUENTIAL TRAPPING OF PLATELETS AND NEUTROPHILS IN PULMONARY MICROCIRCULATION IN RATS

We previously showed that endothelin-1 (ET-1) causes accumulation of l eukocytes in the pulmonary microvasculature and increases vascular per meability in isolated rat lungs provided the presence of leukocytes in the perfusate, In the present study we examined the time sequence for morphological changes induced by ET-1 in rat alveolar tissue. For thi s purpose we used morphometric analysis based on lung transmission ele ctron micrographs. Morphometry was performed by point counting, and da ta were expressed as relative volume density. ET-1 (0.06, 0.6, and 6 n mol/kg) was infused-into the internal jugular vein, and the animals we re killed at certain points of time, The lungs were fixed by endotrach eal instillation of McDowell's fixative. Infusion of ET-1 (0.06 of 0.6 nmol/kg) caused no significant morphological changes in the rat alveo lar tissue as assessed by morphometric examination. A sevenfold increa se in volume density of platelets was seen 5 min after infusion of ET- 1, 6 nmol/kg. The platelets were loosely aggregated, adhered partly to the endothelium, and some of them had a spherical shape with vacuoles , indicating activation. The volume density of erythrocytes increased threefold, lasting 30 min. At 120 min, the volume density of polymorph onuclear leukocytes (PMN) increased 10- fold. The PMN adhered closely to the endothelium and partly occluded the capillary lumen. Simultaneo usly: the endothelial cell surface showed morphological signs of injur y. No significant changes were observed in the volume density of alveo lar macrophages or monocytes. No significant changes were seen in lung volumes or the volume of the alveolar tissue compartment, The results showed that ET-1 causes a time- and dose-dependent sequential entrapm ent of platelets and neutrophils in the pulmonary circulation.