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Endogenous Asymmetric Dimethylarginine Pathway in High Altitude Adapted Yaks.

Mizuno S, Ishizaki T, Toga H, Sakai A, Isakova J, Taalaibekova E, Baiserkeev Z, Kojonazarov B, Aldashev A - Biomed Res Int (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, Kanazawa Medical University, Ishikawa 920-0293, Japan.

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.

No MeSH data available.


Related in: MedlinePlus

Western blot analysis of eNOS, DDAH I, and DDAH II protein in lungs from yaks and bovines. The photomicrograph shown is a representative image from the experiments, and the bar graph shows the density ratios of eNOS, DDAH I, and DDAH II protein bands relative to those from bovines. The eNOS, DDAH I, and DDAH II protein expression was apparently increased in lungs from yaks compared with those from bovines. Data are expressed as mean ± SD (n = 2).
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fig2: Western blot analysis of eNOS, DDAH I, and DDAH II protein in lungs from yaks and bovines. The photomicrograph shown is a representative image from the experiments, and the bar graph shows the density ratios of eNOS, DDAH I, and DDAH II protein bands relative to those from bovines. The eNOS, DDAH I, and DDAH II protein expression was apparently increased in lungs from yaks compared with those from bovines. Data are expressed as mean ± SD (n = 2).

Mentions: The Western blot analysis of lung homogenates showed that the expression of the eNOS protein in the lungs from yaks was markedly higher when compared with that from bovines, and both the DDAH I and DDAH II protein expression were apparently increased in the lungs from yaks when compared with those from bovines (Figure 2).


Endogenous Asymmetric Dimethylarginine Pathway in High Altitude Adapted Yaks.

Mizuno S, Ishizaki T, Toga H, Sakai A, Isakova J, Taalaibekova E, Baiserkeev Z, Kojonazarov B, Aldashev A - Biomed Res Int (2015)

Western blot analysis of eNOS, DDAH I, and DDAH II protein in lungs from yaks and bovines. The photomicrograph shown is a representative image from the experiments, and the bar graph shows the density ratios of eNOS, DDAH I, and DDAH II protein bands relative to those from bovines. The eNOS, DDAH I, and DDAH II protein expression was apparently increased in lungs from yaks compared with those from bovines. Data are expressed as mean ± SD (n = 2).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4563057&req=5

fig2: Western blot analysis of eNOS, DDAH I, and DDAH II protein in lungs from yaks and bovines. The photomicrograph shown is a representative image from the experiments, and the bar graph shows the density ratios of eNOS, DDAH I, and DDAH II protein bands relative to those from bovines. The eNOS, DDAH I, and DDAH II protein expression was apparently increased in lungs from yaks compared with those from bovines. Data are expressed as mean ± SD (n = 2).
Mentions: The Western blot analysis of lung homogenates showed that the expression of the eNOS protein in the lungs from yaks was markedly higher when compared with that from bovines, and both the DDAH I and DDAH II protein expression were apparently increased in the lungs from yaks when compared with those from bovines (Figure 2).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, Kanazawa Medical University, Ishikawa 920-0293, Japan.

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.

No MeSH data available.


Related in: MedlinePlus