Pathology of pulmonary hypertension: a human and experimental study.
To clarify the histopathological characteristics of pulmonary hypertension (PH) in Japan, and to clarify the role of serotonin and endothelin in monocrotaline induced PH, human histopathological studies and experimental studies were carried out. An epidemiological study based on the Annual of the Pathological Autopsy Cases in Japan, and a morphological study on autopsy cases of congenital heart disease and idiopathic PH were performed. Plasma levels of serotonin and endothelin, vascular responsiveness to serotonin, and the effects of a selective serotonin antagonist, DV-7028, were investigated after monocrotaline injection. Plexogenic pulmonary arteriopathy was prevalent, and recurrent pulmonary thromboembolism and pulmonary veno-occlusive disease extremely rare among primary pulmonary hypertension in Japan. In secondary PH, systemic lupus erythematosus and mixed connective tissue disease were frequent and showed particularly severe intimal and medial thickening. After an injection of monocrotaline, plasma serotonin and endothelin levels were raised, and pulmonary arteries showed hyperreactivity to serotonin. DV-7028 (5-HT2 receptor antagonist) attenuated the rise in pulmonary artery pressure and the various effects of monocrotaline. There may be some genetic difference between PH in Japan and other countries. Roles for serotonin and endothelin in the initiation and progression of monocrotaline induced PH are suggested.
Hosoda
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Department of Pathology, School of Medicine, Keio University, Tokyo, Japan.
D000328:Adult; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000453:epidemiology / Q000209:etiology / Q000473:pathology*; D007564:Japan / Q000453:epidemiology; D008297:Male; D008854:Microscopy, Electron; D016686:Monocrotaline; D011651:Pulmonary Artery / Q000473:pathology / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley
D016686:Monocrotaline