Hypoxia and reoxygenation of the lung tissues induced mRNA expressions of superoxide dismutase and catalase and interventions from different antioxidants.
OBJECTIVE
Hypoxic pulmonary vasoconstriction (HPV) is a well-known phenomenon to temporarily offset a ventilation/perfusion mismatch. Sustained HPV may lead to pulmonary hypertension. In this protocol, we studied the relationships between the HPV response and oxygen radical release after hypoxia/reoxygenation (H/R) challenge in an isolated perfused lung model.


METHODS
We used an in situ isolated rat lung preparation. Two hypoxic challenges (5% CO2-95% N2) were administered for 10 minutes each with administration of antioxidants of superoxide dismutase (SOD; 2 mg/kg), catalase (20,000 IU/kg), dimethylthiourea (DMTU; 100 mg/kg), dimethylsulfoxide (DMSO; 1 mL/kg), or allopurinol (30 mg/kg) between 2 challenges. We measured pulmonary arterial pressure changes before, during, and after H/R challenge. We measured blood concentration changes in hydroxyl radicals and nitric oxide (NO) before and after H/R. mRNA expressions of SOD and catalase in lung tissue were measured after the experiments.


RESULTS
Hypoxia induced pulmonary vasoconstriction by increasing pulmonary arterial pressure and consecutive hypoxic challenges did not show tachyphylaxis. Blood concentrations of hydroxyl radicals and NO increased significantly after H/R challenges. mRNA expressions of SOD and catalase increased significantly, however, neither SOD nor catalase showed attenuated effects on HPV responses. Small molecules of DMTU, DMSO, and allopurinol attenuated the HPV responses.


CONCLUSIONS
H/R induced increases in the expressions of SOD and catalase in lung tissues. DMTU, DMSO, and allopurinol antioxidants attenuated the HPV responses by reducing the oxygen radical release.
Shen
C Y
CY
Division of Chest, Weigong Memorial Hospital, Miouli County, Taiwan.
Lee
J F
JF
Su
C L
CL
Wang
D
D
Chen
C F
CF
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000235:genetics*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D000860:Hypoxia / Q000201:enzymology* / Q000235:genetics; D008168:Lung / Q000201:enzymology*; D016133:Polymerase Chain Reaction; D011651:Pulmonary Artery / Q000503:physiopathology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D000975:Antioxidants; D016166:Free Radical Scavengers; D012333:RNA, Messenger; D000493:Allopurinol; C038983:1,3-dimethylthiourea; D002374:Catalase; D013482:Superoxide Dismutase; D013890:Thiourea; D004121:Dimethyl Sulfoxide