Open AccessNitric oxide modulates hypoxic pulmonary smooth muscle cell proliferation and apoptosis by regulating carbon monoxide pathway 1
Author(s) -
WANG Yanfei,
TIAN Hong,
TANG Chaoshu,
JIN Hongfang,
DU Junbao
Publication year - 2007
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2006.00483.x
Subject(s) - nitric oxide , apoptosis , carbon monoxide , microbiology and biotechnology , chemistry , signal transduction , hypoxia (environmental) , nitric oxide synthase , medicine , biology , biochemistry , oxygen , organic chemistry , catalysis
Aim: 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. Conclusion: 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.