title: Nitric oxide modulates hypoxic pulmonary smooth muscle cell proliferation and apoptosis by regulating carbon monoxide pathway.
abstract: OBJECTIVE
  To explore the role of carbon monoxide (CO) in the regulation of hypoxic pulmonary artery smooth muscle cell (PASMC) proliferation and apoptosis by nitric oxide (NO).
  
  
  METHODS
  PASMC of Wistar rats was cultured in vitro in the presence of a NO donor, sodium nitroprusside, or an inhibitor of heme oxygenase (HO), zinc protoporphyrin-IX, or under both normoxic and hypoxic conditions. Nitrite and carboxyhemoglobin in PASMC medium were detected with spectrophotometry. The proliferating and apoptotic percentage of PASMC was measured by flow cytometry. The expression of HO-1 mRNA in PASMC was analyzed by fluorescent real-time quantitative PCR, and the proliferating cell nuclear antigen and caspase-3 were examined by immunocytochemical analysis.
  
  
  RESULTS
  The results showed that hypoxia suppressed NO generation from PASMC, which promoted hypoxic PASMC proliferation and induced apoptosis. Meanwhile, hypoxia induced HO-1 expression in PASMC and promoted CO production from PASMC, which inhibited PASMC proliferation and regulated PASMC apoptosis. NO upregulated the expression of HO-1 mRNA in hypoxic PASMC; NO also inhibited proliferation and promoted apoptosis of hypoxic PASMC, possibly by regulating the production of CO.
  
  
  CONCLUSIONS
  The results indicated that CO could inhibit proliferation and regulate apoptosis of PASMC, and NO inhibited proliferation and promoted apoptosis of hypoxic PASMC, possibly by regulating the production of CO.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Yan-Fei
authors.initials: YF
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Tian
authors.forename: Chao-Shu
authors.initials: CS
authors.lastname: Tang
authors.forename: Hong-Fang
authors.initials: HF
authors.lastname: Jin
authors.forename: Jun-Bao
authors.initials: JB
authors.lastname: Du
mesh_terms: D000818:Animals; D017209:Apoptosis; D002248:Carbon Monoxide / Q000378:metabolism / Q000502:physiology*; D015687:Cell Hypoxia; D049109:Cell Proliferation; D002478:Cells, Cultured; D005434:Flow Cytometry; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D011524:Protoporphyrins / Q000494:pharmacology; D011651:Pulmonary Artery / Q000166:cytology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology
chemical_list: D020030:Nitric Oxide Donors; D011524:Protoporphyrins; D012333:RNA, Messenger; C017803:zinc protoporphyrin; D009599:Nitroprusside; D009569:Nitric Oxide; D002248:Carbon Monoxide; D051547:Heme Oxygenase-1