title: Endogenous Asymmetric Dimethylarginine Pathway in High Altitude Adapted Yaks.
abstract: Hypoxia-induced and high altitude pulmonary hypertension are a major problem in the mountain areas of the world. The asymmetric methylarginines (ADMA) inhibit nitric oxide (NO) synthesis by competing with L-arginine, and high levels of plasma ADMA predict adverse outcomes in pulmonary hypertension. However, little is known about the regulation of the ADMA-NO pathway in animals adapted to high altitudes. We measured the plasma ADMA concentration, endothelial NO synthase (eNOS), dimethylarginine dimethylaminohydrolases (DDAH) protein expression, and DDAH activities in the lungs from yaks. Although the yaks are hypoxemic, cardiac function and pulmonary arterial pressures are almost normal, and we found decreased DDAH expression and activity in association with reduced plasma ADMA concentrations. The eNOS expression was significantly higher in yaks. These results indicate that augmented endogenous NO activity in yaks through the ADMA-DDAH pathway and eNOS upregulation account for the low pulmonary vascular tone observed in high altitude adapted yaks.
authors.affiliation: Department of Respiratory Medicine, Kanazawa Medical University, Ishikawa 920-0293, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Mizuno
authors.affiliation: Department of Respiratory Medicine, Kanazawa Medical University, Ishikawa 920-0293, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ishizaki
authors.affiliation: Department of Respiratory Medicine, Kanazawa Medical University, Ishikawa 920-0293, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Toga
authors.affiliation: Department of Health Science, Matsumoto University, Matsumoto 390-1295, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Sakai
authors.affiliation: Laboratory of Molecular and Cell Biology, Institute of Molecular Biology and Medicine, 720040 Bishkek, Kyrgyzstan.
authors.forename: Jainagul
authors.initials: J
authors.lastname: Isakova
authors.affiliation: Laboratory of Molecular and Cell Biology, Institute of Molecular Biology and Medicine, 720040 Bishkek, Kyrgyzstan.
authors.forename: Elnura
authors.initials: E
authors.lastname: Taalaibekova
authors.affiliation: Laboratory of Molecular and Cell Biology, Institute of Molecular Biology and Medicine, 720040 Bishkek, Kyrgyzstan.
authors.forename: Zamirbek
authors.initials: Z
authors.lastname: Baiserkeev
authors.affiliation: Laboratory of Molecular and Cell Biology, Institute of Molecular Biology and Medicine, 720040 Bishkek, Kyrgyzstan ; Excellence Cluster Cardio-Pulmonary System, Universities of Giessen & Marburg Lung Center, 35392 Giessen, Germany.
authors.forename: Baktybek
authors.initials: B
authors.lastname: Kojonazarov
authors.affiliation: Laboratory of Molecular and Cell Biology, Institute of Molecular Biology and Medicine, 720040 Bishkek, Kyrgyzstan.
authors.forename: Almaz
authors.initials: A
authors.lastname: Aldashev
mesh_terms: D000222:Adaptation, Physiological; D000531:Altitude; D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D002417:Cattle; D006439:Hemodynamics; D008168:Lung / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism
chemical_list: D009566:Nitrates; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D052250:Nitric Oxide Synthase Type III; D000581:Amidohydrolases; C059999:dimethylargininase