PMID- 30911278 OWN - NLM STAT- MEDLINE DCOM- 20190724 LR - 20200225 IS - 1449-1907 (Electronic) IS - 1449-1907 (Linking) VI - 16 IP - 3 DP - 2019 TI - Decreased Ambient Oxygen Tension Alters the Expression of Endothelin-1, iNOS and cGMP in Rat Alveolar Macrophages. PG - 443-449 LID - 10.7150/ijms.28353 [doi] AB - Background: Hypoxia plays an important role in the vascular tone of pulmonary circulation via the vasculature and parenchymal tissue. Endothelin-1 (ET-1), a potent vasoconstrictive peptide, plays a role in inflammation in mononuclear cells. Nitric oxide synthase (NOS), which generates nitric oxide (NO)/cyclic 3', 5'-monophosphate (cGMP), is coexpressed with ET-1 in many cell types. The aim of this study was to assess whether hypoxia induces the production of ET-1 and associated expression of NOS, NO/cGMP and chemokines in rat alveolar macrophages (AMs). Methods: NR8383 cells were cultured under hypoxic (1% oxygen) conditions for 0, 2, 4, 8 and 12 hours. Levels of ET-1, inducible NOS (iNOS), phosphorylated iNOS (p-iNOS), nitrite/nitrate (NOx), cGMP and monocyte chemoattractant protein-1 (MCP-1) were measured. Results: ET-1, p-iNOS, NOx, and cGMP increased significantly in AMs after 4 hours of hypoxia (p < 0.05). ET-1 and MCP-1 mRNA increased after 8 hours (p < 0.05). The protein expression of ET-1, MCP-1, and p-iNOS increased in a time-dependent manner, while iNOS expression decreased with time. Conclusions: The changes in ET-1, p-iNOS, and the NO/cGMP pathway in AMs may help elucidate the mechanisms in the hypoxic lung. Understanding changes in the endothelin axis in hypoxic AMs is a crucial first step to unravel its role in pulmonary circulation. FAU - Chen, I-Chen AU - Chen IC AD - Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. AD - Department of Pediatrics, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. AD - Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. FAU - Lin, Yu-Tsai AU - Lin YT AD - Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. FAU - Huang, Jhy-Shrian AU - Huang JS AD - Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. FAU - Wu, Bin-Nan AU - Wu BN AD - Department of Pharmacology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. FAU - Hsu, Jong-Hau AU - Hsu JH AD - Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. AD - Department of Pediatrics, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. FAU - Tan, Mian-Shin AU - Tan MS AD - Department of Biomedical Science and Environmental Biology, College of Life Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan. FAU - Dai, Zen-Kong AU - Dai ZK AD - Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. AD - Department of Pediatrics, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. LA - eng PT - Journal Article DEP - 20190228 PL - Australia TA - Int J Med Sci JT - International journal of medical sciences JID - 101213954 RN - 0 (Ccl2 protein, rat) RN - 0 (Chemokine CCL2) RN - 0 (Endothelin-1) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.13.39 (Nos2 protein, rat) RN - H2D2X058MU (Cyclic GMP) MH - Animals MH - Cell Hypoxia MH - Cells, Cultured MH - Chemokine CCL2/genetics/metabolism MH - Cyclic GMP/*metabolism MH - Endothelin-1/genetics/*metabolism MH - Gene Expression Regulation MH - Macrophages, Alveolar/*metabolism MH - Nitric Oxide/metabolism MH - Nitric Oxide Synthase Type II/genetics/*metabolism MH - Rats, Sprague-Dawley PMC - PMC6428981 OTO - NOTNLM OT - alveolar macrophage OT - endothelin-1 OT - hypoxia OT - nitric oxide synthase COIS- Competing Interests: The authors have declared that no competing interest exists. EDAT- 2019/03/27 06:00 MHDA- 2019/07/25 06:00 PMCR- 2019/01/01 CRDT- 2019/03/27 06:00 PHST- 2018/07/06 00:00 [received] PHST- 2018/12/28 00:00 [accepted] PHST- 2019/03/27 06:00 [entrez] PHST- 2019/03/27 06:00 [pubmed] PHST- 2019/07/25 06:00 [medline] PHST- 2019/01/01 00:00 [pmc-release] AID - ijmsv16p0443 [pii] AID - 10.7150/ijms.28353 [doi] PST - epublish SO - Int J Med Sci. 2019 Feb 28;16(3):443-449. doi: 10.7150/ijms.28353. eCollection 2019.