start-ver=1.4
cd-journal=joma
no-vol=4
cd-vols=
no-issue=6
article-no=
start-page=572
end-page=576
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2008
dt-pub=200811
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Hemin Treatment Abrogates Monocrotaline-Induced Pulmonary Hypertension
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Treatment of rats with monocrotaline (MCT), a pyrrolizidine alkaloid plant toxin, is known to cause pulmonary hypertension (PH), and it has been used as a useful experimental model of PH. Recent findings suggested that pulmonary inflammation may play a significant role in the pathogenesis of MCT-induced PH. We also demonstrated that, following MCT administration to rats, there was a significant and sustained increase in the pulmonary expression of heme oxygenase-1 (HO-1), which is known to be induced by various oxidative stresses, including inflammation and free heme, and is thought to be essential in the protection against oxidative tissue injuries. In this study, we administered hemin (ferriprotoporphyrin chloride, 30 mol/kg b.w., subcutaneously), a potent inducer of HO-1, every 3 days to rats following subcutaneous administration of MCT (60 mg/kg) and examined its effect on MCT-induced PH and pulmonary inflammation. MCT administration caused pulmonary arterial wall thickening with marked elevation of right ventricular pressure, in association with prominent pulmonary inflammation as revealed by the increase in gene expression of tumor necrosis factor-alpha and the number of infiltrated neutrophils in the lung. In contrast, hemin treatment of MCT-administered animals, which led to a further increase in pulmonary HO-1 mRNA expression, significantly ameliorated MCT-induced PH as well as tissue inflammation. These findings suggest that hemin treatment ameliorates MCT-induced PH possibly mediated through induction of pulmonary HO-1 which leads to the attenuation of pulmonary inflammation.
en-copyright=
kn-copyright=

en-aut-name=ShimzuK.
en-aut-sei=Shimzu
en-aut-mei=K.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TakahashiT.
en-aut-sei=Takahashi
en-aut-mei=T.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=IwasakiT.
en-aut-sei=Iwasaki
en-aut-mei=T.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ShimizuH.
en-aut-sei=Shimizu
en-aut-mei=H.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=InoueK.
en-aut-sei=Inoue
en-aut-mei=K.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MorimatsuH.
en-aut-sei=Morimatsu
en-aut-mei=H.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=OmoriE.
en-aut-sei=Omori
en-aut-mei=E.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=MatsumiM.
en-aut-sei=Matsumi
en-aut-mei=M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=AkagiR.
en-aut-sei=Akagi
en-aut-mei=R.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=MoritaK.
en-aut-sei=Morita
en-aut-mei=K.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=
kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Anesthesiol & Resuscitol

affil-num=2
en-affil=
kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Anesthesiol & Resuscitol

affil-num=3
en-affil=
kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Anesthesiol & Resuscitol

affil-num=4
en-affil=
kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Anesthesiol & Resuscitol

affil-num=5
en-affil=
kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Anesthesiol & Resuscitol

affil-num=6
en-affil=
kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Anesthesiol & Resuscitol

affil-num=7
en-affil=
kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Anesthesiol & Resuscitol

affil-num=8
en-affil=
kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Anesthesiol & Resuscitol

affil-num=9
en-affil=
kn-affil=Okayama Prefectural Univ, Dept Nutr Sci

affil-num=10
en-affil=
kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Anesthesiol & Resuscitol
en-keyword=Heme oxygenase-1
kn-keyword=Heme oxygenase-1
en-keyword=hemin
kn-keyword=hemin
en-keyword=inflammation
kn-keyword=inflammation
en-keyword=monocrotaline
kn-keyword=monocrotaline
en-keyword=pulmonary hypertension
kn-keyword=pulmonary hypertension
en-keyword=tumor necrosis factor-alpha
kn-keyword=tumor necrosis factor-alpha
END