A Morphological Study of the Pulmonary Endothelium and Neuroendocrine Cells in Monocrotaline-Induced Pulmonary Arterial Hypertension

ABSTRACT

To investigate the mechanism of monocrotaline-induced pulmonary arterial hypertension, authors performed immunohistochemical study using antibody to von Willebrand factor(vWF), cell kinetic study using 5-bromodeoxyuridine and ultrastructural study after single subcutaneous injection of monocrotaline(MCT) to Wistar rats. The results of this study demonstrated that the expression of vWF by pulmonary endothelial cells was markedly increased from day 3 until 2 months after MCT injection. The labeling index of pulmonary microvessel endothelium began to increase after six days and was maximal on the third weeks, and thereafter it remained slightly increased above basal level. Electron microscopic study revealed attachment of inflammatory cells an platelets to endothelium from 6 hours and degranulation of attached platelets 24 hours after MCT injection. Evidences of endothelial injury began to appear from 12 hours after MCT injection. Evidences of endothelial injury began to appear from 12 hours and was maximal after 48 hours. From the third day, ultrastructural change of cell regeneration and hypertrophy began to appear and was continuosly observed until 2 months. In addition, we evaluated the changes in the number of pulmonary neuroendocrine cells using antibody to gastrin releasing peptide but it demonstrated no change until 2 months suggesting no role of neuroendocrine cells in the development of pulmonary hypertension of Wistar rats at early stage. In conclusion, the results indicate that pulmonary hypertension by MCT injection is due to increased vascular resistance caused by vasoconstriction and hyperplasia of endothelium with musculariz ation of the pulmonary arterioles induced by endothelial dysfunction and some biologic substances released form endothelium and platelets.