PMID- 30186602 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220321 IS - 1674-9782 (Print) IS - 2049-1891 (Electronic) IS - 1674-9782 (Linking) VI - 9 DP - 2018 TI - N-carbamylglutamate restores nitric oxide synthesis and attenuates high altitude-induced pulmonary hypertension in Holstein heifers ascended to high altitude. PG - 63 LID - 10.1186/s40104-018-0277-6 [doi] LID - 63 AB - 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. FAU - Wang, Shuxiang AU - Wang S AD - 1State 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 University, Beijing, 100193 People's Republic of China. ISNI: 0000 0004 0530 8290. GRID: grid.22935.3f FAU - Azarfar, Arash AU - Azarfar A AD - 2Faculty of Agriculture, Department of Animal Science, Lorestan University, PO Box 465, Khorramabad, Iran. ISNI: 0000 0004 1757 0173. GRID: grid.411406.6 FAU - Wang, Yajing AU - Wang Y AD - 1State 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 University, Beijing, 100193 People's Republic of China. ISNI: 0000 0004 0530 8290. GRID: grid.22935.3f FAU - Cao, Zhijun AU - Cao Z AD - 1State 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 University, Beijing, 100193 People's Republic of China. ISNI: 0000 0004 0530 8290. GRID: grid.22935.3f FAU - Li, Shengli AU - Li S AD - 1State 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 University, Beijing, 100193 People's Republic of China. ISNI: 0000 0004 0530 8290. GRID: grid.22935.3f LA - eng PT - Journal Article DEP - 20180903 PL - England TA - J Anim Sci Biotechnol JT - Journal of animal science and biotechnology JID - 101581293 PMC - PMC6120069 OTO - NOTNLM OT - High-altitude pulmonary hypertension OT - Holstein heifers OT - N-carbamylglutamate OT - Tibet COIS- All protocols for sampling and handling of animals were approved by the Institutional Animal Care and Use Committee at China Agricultural University (Beijing, P. R. China). The experiment was conducted according to the regulations and guidelines established by this committee.Not applicable.The authors declare that they have no competing interests. EDAT- 2018/09/07 06:00 MHDA- 2018/09/07 06:01 PMCR- 2018/09/03 CRDT- 2018/09/07 06:00 PHST- 2018/03/13 00:00 [received] PHST- 2018/07/03 00:00 [accepted] PHST- 2018/09/07 06:00 [entrez] PHST- 2018/09/07 06:00 [pubmed] PHST- 2018/09/07 06:01 [medline] PHST- 2018/09/03 00:00 [pmc-release] AID - 277 [pii] AID - 10.1186/s40104-018-0277-6 [doi] PST - epublish SO - J Anim Sci Biotechnol. 2018 Sep 3;9:63. doi: 10.1186/s40104-018-0277-6. eCollection 2018.