Heme oxygenase-1 reduces murine monocrotaline-induced pulmonary inflammatory responses and resultant right ventricular overload.
Monocrotaline (MT), a pyrrolizidine alkaloid, causes pulmonary hypertension (PH) in rats and is widely utilized to analyze the pathophysiology of PH. However, a murine PH model with which transgenic animals may be used has not been established. To establish a murine MT-induced PH model, we administered different amounts of MT and determined the extent of right ventricular (RV) overload and PH. We also examined the expression of heme oxygenase-1 (HO-1), a potential antistress protein in MT-treated animals, and evaluated the functional role of HO-1 by administering an HO-1 inhibitor. Significant pulmonary inflammation and RV hypertrophy were observed when mice were given 600 mg/kg weight of MT weekly for 8 weeks. In addition, elevated RV pressure and induction of HO-1 in lung and RV were observed with this dose of MT. Interestingly, inhibition of HO activity promoted inflammatory changes in the lung and the resultant RV hypertrophy. HO-1 may play defensive roles against murine MT-induced pulmonary inflammation and the resultant RV overload.
Goto
Jun
J
First Department of Internal Medicine, Fukushima Medical University, Fukushima, Japan.
Ishikawa
Kazunobu
K
Kawamura
Keiichi
K
Watanabe
Yasuyuki
Y
Matumoto
Hayato
H
Sugawara
Daisuke
D
Maruyama
Yukio
Y
D000818:Animals; D001835:Body Weight; D006332:Cardiomegaly; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000378:metabolism; D006352:Heart Ventricles / Q000201:enzymology / Q000473:pathology; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology*; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology*; D008168:Lung / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D016686:Monocrotaline / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D051381:Rats; D013314:Stress, Mechanical; D016278:Ventricular Function, Right
D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D016686:Monocrotaline; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse