title: Inhibition of inducible nitric oxide synthase expression and nitric oxide production in plateau pika (Ochotona curzoniae) at high altitude on Qinghai-Tibet Plateau.
abstract: Nitric oxide (NO), a potent vasodilator, plays an important role in preventing hypoxia induced pulmonary hypertension. Endogenous NO is synthesized by nitric oxide synthases (NOSs) from l-arginine. In mammals, three different NOSs have been identified, including neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS). Plateau pika (Ochotona curzoniae) is a typical hypoxia tolerant mammal that lives at 3000-5000 m above sea level on the Qinghai-Tibet Plateau. The aim of this study was to investigate whether NOS expression and NO production are regulated by chronic hypoxia in plateau pika. Quantitative real-time PCR and western blot analyses were conducted to quantify relative abundances of iNOS and eNOS transcripts and proteins in the lung tissues of plateau pikas at different altitudes (4550, 3950 and 3200 m). Plasma NO metabolites, nitrite/nitrate (NO(x)⁻) levels were also examined by Ion chromatography to determine the correlation between NO production and altitude level. The results revealed that iNOS transcript levels were significantly lower in animals at high altitudes (decreased by 53% and 57% at altitude of 3950 and 4550 m compared with that at 3200 m). Similar trends in iNOS protein abundances were observed (26% and 41% at 3950 and 4550 m comparing with at 3200 m). There were no significant differences in eNOS mRNA and protein levels in the pika lungs among different altitudes. The plasma NO(x)⁻ levels of the plateau pikas at high altitudes significantly decreased (1.65±0.19 μg/mL at 3200 m to 0.44±0.03 μg/mL at 3950 m and 0.24±0.01 μg/mL at 4550 m). This is the first evidence describing the effects of chronic hypoxia on NOS expression and NO levels in the plateau pika in high altitude adaptation. We conclude that iNOS expression and NO production are suppressed at high altitudes, and the lower NO concentration at high altitudes may serve crucial roles for helping the plateau pika to survive at hypoxic environment.
authors.affiliation: Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, China; Key Laboratory of Crop Molecular Breeding, Xining, Qinghai Province, China; University of Chinese Academy of Sciences, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Xie
authors.affiliation: Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, China.
authors.forename: Xuze
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Animal Sciences, College of Agriculture and Animal Husbandry, Qinghai University, Xining, China.
authors.forename: Delin
authors.initials: D
authors.lastname: Qi
authors.affiliation: Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, China; University of Chinese Academy of Sciences, China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Guo
authors.affiliation: Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, China; University of Chinese Academy of Sciences, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Pang
authors.affiliation: School of Life and Geography Science, Qinghai Normal University, Xining, China.
authors.forename: Yurong
authors.initials: Y
authors.lastname: Du
authors.affiliation: Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zou
authors.affiliation: Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, China; Key Laboratory of Crop Molecular Breeding, Xining, Qinghai Province, China. Electronic address: guo@nwipb.cas.cn.
authors.forename: Songchang
authors.initials: S
authors.lastname: Guo
authors.affiliation: Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, China. Electronic address: xqzhao@nwipb.cas.cn.
authors.forename: Xinquan
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000531:Altitude; D000818:Animals; D015971:Gene Expression Regulation, Enzymologic; D000860:Hypoxia / Q000097:blood / Q000201:enzymology / Q000235:genetics; D007793:Lagomorpha / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000201:enzymology / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis* / Q000235:genetics; D018609:Tibet
chemical_list: D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II
keywords: Endothelial nitric oxide synthase; Inducible nitric oxide synthase; Nitric oxide; Plateau pika; Qinghai-Tibet Plateau