Endothelin-1 causes accumulation of leukocytes in the pulmonary circulation.

Abstract

We previously reported that the endothelin-1 (ET-1)-induced increase in microvascular permeability in isolated rat lungs required leukocytes in the perfusate. The present study examines whether intravenous administration of ET-1 in rats causes an inflammatory reaction in the lungs. Histological examination of the lung specimens 2 hr following ET-1 infusion showed adhesion of leukocytes to the vascular endothelium in pulmonary vessels and sequestration of leukocytes in the pulmonary capillaries. Microscopic examination of the bronchoalveolar lavage fluid revealed that leukocytes had migrated into the alveoli. Simultaneously a depletion of peripheral blood leukocytes was observed. These effects were reversible by 24 hr. Monitoring of systemic hemodynamic effects showed a continued reduced cardiac stroke volume and increasing heart rate after 2 hr. In isolated rat lungs, ET-1 caused a rapid increase in pulmonary artery pressure, pulmonary microvascular pressure, and edema formation. Compared with Krebs-albumin-perfused lungs, blood-perfusion accelerated the edemagenic effect of ET-1. ET-1 plays a role in the regulation of leukocyte-endothelial cell interactions in the pulmonary circulation. This has potential importance for the edemagenic effect of ET-1.