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Antioxid Redox Signal. 2002 Aug;4(4):563-8.

Heme oxygenase-1 reduces murine monocrotaline-induced pulmonary inflammatory responses and resultant right ventricular overload.

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1
First Department of Internal Medicine, Fukushima Medical University, Fukushima, Japan.

Abstract

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.

PMID:
12230867
DOI:
10.1089/15230860260220058
[Indexed for MEDLINE]

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