N-carbamylglutamate restores nitric oxide synthesis and attenuates high altitude-induced pulmonary hypertension in Holstein heifers ascended to high altitude
Abstract Background High-altitude pulmonary hypertension (HAPH) is a life-threating condition for animals in high altitude, and disturbance of endothelial nitric oxide (NO) synthesis contributes to its pathogenesis. N-carbamylglutamate (NCG), which enhances arginine synthesis, promotes endogenous sy...
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doaj-07c290977e81441b8ab55264f4eba65d2020-11-24T21:29:49ZengBMCJournal of Animal Science and Biotechnology2049-18912018-09-01911810.1186/s40104-018-0277-6N-carbamylglutamate restores nitric oxide synthesis and attenuates high altitude-induced pulmonary hypertension in Holstein heifers ascended to high altitudeShuxiang Wang0Arash Azarfar1Yajing Wang2Zhijun Cao3Shengli Li4State Key Laboratory of Animal Nutrition, Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, College of Animal Science and Technology, China Agricultural UniversityFaculty of Agriculture, Department of Animal Science, Lorestan UniversityState Key Laboratory of Animal Nutrition, Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, College of Animal Science and Technology, China Agricultural UniversityState Key Laboratory of Animal Nutrition, Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, College of Animal Science and Technology, China Agricultural UniversityState Key Laboratory of Animal Nutrition, Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, College of Animal Science and Technology, China Agricultural UniversityAbstract Background High-altitude pulmonary hypertension (HAPH) is a life-threating condition for animals in high altitude, and disturbance of endothelial nitric oxide (NO) synthesis contributes to its pathogenesis. N-carbamylglutamate (NCG), which enhances arginine synthesis, promotes endogenous synthesis of NO. In this study, we determined the effects of NCG on alleviating HAPH in Holstein heifers that ascended to Tibet (Lhasa, 3,658 m). Methods Exp. 1, 2,000 Holstein heifers were transported from low elevation (1,027 m) to Lhasa. After being exposed to hypoxia for 1 yr, Holstein heifers were assigned to a healthy group (Control, n = 6) with mean pulmonary hypertension (mPAP) < 41 mmHg, and an HAPH affected group (HAPH, n = 6) with mPAP > 49 mmHg. Lung tissues were collected to evaluate histopathological changes and the expression of endothelial nitric oxide synthase (eNOS). Exp. 2, ten healthy heifers and 10 HAPH affected heifers were supplemented with NCG (20 g/d per heifer) for 4 wk. Physiological parameters were determined and blood samples were collected on d − 1 and d 28 of the feeding trial. Results Expression of eNOS in small pulmonary arteriole intima was higher in the healthy than HAPH group (P = 0.006), whereas HAPH group had significantly thicker media and adventitia than healthy group (all P < 0.05). The mRNA of eNOS and protein level of eNOS were higher in the lungs of heifers in the healthy group than in the HAPH group (both P < 0.001), whereas endothelin-1 protein levels were higher in HAPH group than in the healthy group (P = 0.025). NCG supplementation decreased mPAP and ammonia (both P = 0.001), whereas it increased the expression of eNOS, arginine, and plasma NO (all P < 0.05). Conclusions The expression of eNOS was decreased in Holstein heifers with HAPH. NCG supplementation decreased mPAP through the restoration of eNOS and endogenous NO synthesis.http://link.springer.com/article/10.1186/s40104-018-0277-6High-altitude pulmonary hypertensionHolstein heifersN-carbamylglutamateTibet |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shuxiang Wang Arash Azarfar Yajing Wang Zhijun Cao Shengli Li |
spellingShingle |
Shuxiang Wang Arash Azarfar Yajing Wang Zhijun Cao Shengli Li N-carbamylglutamate restores nitric oxide synthesis and attenuates high altitude-induced pulmonary hypertension in Holstein heifers ascended to high altitude Journal of Animal Science and Biotechnology High-altitude pulmonary hypertension Holstein heifers N-carbamylglutamate Tibet |
author_facet |
Shuxiang Wang Arash Azarfar Yajing Wang Zhijun Cao Shengli Li |
author_sort |
Shuxiang Wang |
title |
N-carbamylglutamate restores nitric oxide synthesis and attenuates high altitude-induced pulmonary hypertension in Holstein heifers ascended to high altitude |
title_short |
N-carbamylglutamate restores nitric oxide synthesis and attenuates high altitude-induced pulmonary hypertension in Holstein heifers ascended to high altitude |
title_full |
N-carbamylglutamate restores nitric oxide synthesis and attenuates high altitude-induced pulmonary hypertension in Holstein heifers ascended to high altitude |
title_fullStr |
N-carbamylglutamate restores nitric oxide synthesis and attenuates high altitude-induced pulmonary hypertension in Holstein heifers ascended to high altitude |
title_full_unstemmed |
N-carbamylglutamate restores nitric oxide synthesis and attenuates high altitude-induced pulmonary hypertension in Holstein heifers ascended to high altitude |
title_sort |
n-carbamylglutamate restores nitric oxide synthesis and attenuates high altitude-induced pulmonary hypertension in holstein heifers ascended to high altitude |
publisher |
BMC |
series |
Journal of Animal Science and Biotechnology |
issn |
2049-1891 |
publishDate |
2018-09-01 |
description |
Abstract Background High-altitude pulmonary hypertension (HAPH) is a life-threating condition for animals in high altitude, and disturbance of endothelial nitric oxide (NO) synthesis contributes to its pathogenesis. N-carbamylglutamate (NCG), which enhances arginine synthesis, promotes endogenous synthesis of NO. In this study, we determined the effects of NCG on alleviating HAPH in Holstein heifers that ascended to Tibet (Lhasa, 3,658 m). Methods Exp. 1, 2,000 Holstein heifers were transported from low elevation (1,027 m) to Lhasa. After being exposed to hypoxia for 1 yr, Holstein heifers were assigned to a healthy group (Control, n = 6) with mean pulmonary hypertension (mPAP) < 41 mmHg, and an HAPH affected group (HAPH, n = 6) with mPAP > 49 mmHg. Lung tissues were collected to evaluate histopathological changes and the expression of endothelial nitric oxide synthase (eNOS). Exp. 2, ten healthy heifers and 10 HAPH affected heifers were supplemented with NCG (20 g/d per heifer) for 4 wk. Physiological parameters were determined and blood samples were collected on d − 1 and d 28 of the feeding trial. Results Expression of eNOS in small pulmonary arteriole intima was higher in the healthy than HAPH group (P = 0.006), whereas HAPH group had significantly thicker media and adventitia than healthy group (all P < 0.05). The mRNA of eNOS and protein level of eNOS were higher in the lungs of heifers in the healthy group than in the HAPH group (both P < 0.001), whereas endothelin-1 protein levels were higher in HAPH group than in the healthy group (P = 0.025). NCG supplementation decreased mPAP and ammonia (both P = 0.001), whereas it increased the expression of eNOS, arginine, and plasma NO (all P < 0.05). Conclusions The expression of eNOS was decreased in Holstein heifers with HAPH. NCG supplementation decreased mPAP through the restoration of eNOS and endogenous NO synthesis. |
topic |
High-altitude pulmonary hypertension Holstein heifers N-carbamylglutamate Tibet |
url |
http://link.springer.com/article/10.1186/s40104-018-0277-6 |
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