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Treatment of Mice with Cobalt Protoporphyrin, an Inducer of Heme Oxygenase and ecSOD, Prevents the Development of Pulmonary Hypertension Caused by Chronic Hypoxia
Author(s) -
Alhawaj Raed,
Ahmad Mansoor,
Remond Mathieu,
Patel Dhara,
Kaminski Pawel M,
Eisenberg Leonard M,
Wolin Michael S
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1034.11
Subject(s) - copp , hypoxia (environmental) , heme oxygenase , pulmonary hypertension , ventricle , medicine , protoporphyrin , endocrinology , pulmonary artery , oxygen tension , chemistry , cardiology , heme , oxygen , biochemistry , porphyrin , organic chemistry , enzyme
Endothelium removed bovine pulmonary arteries (BPA) contract in the presence of hypoxia through removal of a basal relaxation mediated by superoxide (O 2 − ) derived peroxide (H 2 O 2 ). Previous studies from our laboratory have also shown that induction of heme oxygenase 1 (HO‐1) increases extracellular superoxide dismutase (ecSOD) expression leading to an attenuation in hypoxic pulmonary constriction (HPV). Therefore, we hypothesized that cobalt protoporphyrin (CoPP) mediated induction of HO‐1 and ecSOD could have a beneficial effect in attenuating on development of pulmonary hypertension caused by chronic hypoxia. In our current study mice exposed to 21 day hypoxia (10% oxygen) showed a significant increase in pulmonary artery pressure measured through echo doppler pulmonary artery flow, based on ratios of pulmonary acceleration time as a function of ejection time. This increase in pressure was prevented in mice treated with CoPP (3 mg/kg/wk sc), beginning 1 day before exposure to hypoxia. Right ventricle to left ventricle plus septum weight ratios were also attenuated by the CoPP‐treatment. Therfore, CoPP prevents development of pulmonary hypertension caused by exposure to 21 days of hypoxia. Supported by NIH grants HL31069, HL43023 and HL66331.