Comparative effects of isosorbide dinitrate, prednisolone, indomethacin, and elastase on the development of monocrotaline-induced pulmonary hypertension.
The pathogenesis of monocrotaline-induced pulmonary hypertension is not clear. Progressive pulmonary arteritis leading to vascular sclerosis, narrowing of the lumina, and thrombosis is the suspected sequence. To investigate this, we examined the effect of isosorbide dinitrate (ISDN), prednisolone, indomethacin, and elastase in 100 SD male rats, 4 weeks after the injection of monocrotaline (MCT) by cardiac catheterization, right ventricle-to-left ventricle plus septum weight ratio (RV/LV + S), histology, and electron microscopy. ISDN, a vasodilator, reduced the elevation of right ventricular (RV) pressure, RV/LV + S, and also pulmonary vascular remodeling; the characteristic histological feature was dilatation of small pulmonary arteries. Both prednisolone and indomethacin reduced RV pressure, RV/LV + S, and pulmonary vasculitis. Elastase, a protease which controls the metabolism of elastin in the arterial wall, likewise reduced RV pressure, RV/LV + S, and pulmonary vascular remodeling, with a significant decrease in elastosis of the small pulmonary arteries histologically. We concluded that all of the pathological processes resulting from arteritis are important in the development of MCT-induced pulmonary hypertension. In all experimental groups, decreased histopathologic changes correlated with decrease in the pressure. Elastase, which reduces pulmonary arterial sclerosis, is suggested as a new agent to treat pulmonary hypertension.
Kato
T
T
Department of Pathology, Yokohama City University School of Medicine, Japan.
Kitamura
H
H
Kanisawa
M
M
D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology; D007213:Indomethacin / Q000494:pharmacology*; D007548:Isosorbide Dinitrate / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D016686:Monocrotaline; D010196:Pancreatic Elastase / Q000494:pharmacology*; D010947:Plants, Toxic; D011239:Prednisolone / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects; D011763:Pyrrolizidine Alkaloids; D051381:Rats; D011919:Rats, Inbred Strains; D012674:Senecio
D011763:Pyrrolizidine Alkaloids; D016686:Monocrotaline; D011239:Prednisolone; D010196:Pancreatic Elastase; D007548:Isosorbide Dinitrate; D007213:Indomethacin