Wang Shuxiang, Azarfar Arash, Wang Yajing, Cao Zhijun, Li Shengli
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.
2Faculty of Agriculture, Department of Animal Science, Lorestan University, PO Box 465, Khorramabad, Iran.
J Anim Sci Biotechnol. 2018 Sep 3;9:63. doi: 10.1186/s40104-018-0277-6. eCollection 2018.
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).
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, = 6) with mean pulmonary hypertension (mPAP) < 41 mmHg, and an HAPH affected group (HAPH, = 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.
Expression of eNOS in small pulmonary arteriole intima was higher in the healthy than HAPH group ( = 0.006), whereas HAPH group had significantly thicker media and adventitia than healthy group (all < 0.05). The mRNA of and protein level of eNOS were higher in the lungs of heifers in the healthy group than in the HAPH group (both < 0.001), whereas endothelin-1 protein levels were higher in HAPH group than in the healthy group ( = 0.025). NCG supplementation decreased mPAP and ammonia (both = 0.001), whereas it increased the expression of eNOS, arginine, and plasma NO (all < 0.05).
The expression of eNOS was decreased in Holstein heifers with HAPH. NCG supplementation decreased mPAP through the restoration of eNOS and endogenous NO synthesis.
高原肺动脉高压（HAPH）对高原地区的动物来说是一种危及生命的疾病，内皮一氧化氮（NO）合成紊乱是其发病机制之一。N-氨甲酰谷氨酸（NCG）可增强精氨酸合成，促进内源性NO的合成。在本研究中，我们测定了NCG对缓解升至西藏（拉萨，海拔3658米）的荷斯坦小母牛HAPH的影响。
实验1，将2000头荷斯坦小母牛从低海拔地区（1027米）运至拉萨。在暴露于低氧环境1年后，将荷斯坦小母牛分为平均肺动脉压（mPAP）<41mmHg的健康组（对照组，n = 6）和mPAP>49mmHg的HAPH患病组（n = 6）。收集肺组织以评估组织病理学变化和内皮型一氧化氮合酶（eNOS）的表达。实验2，对10头健康小母牛和10头HAPH患病小母牛补充NCG（每头小母牛20克/天），持续4周。在饲养试验的第-1天和第28天测定生理参数并采集血样。
健康组小肺动脉内膜中eNOS的表达高于HAPH组（P = 0.006），而HAPH组的中膜和外膜明显比健康组厚（均P<0.05）。健康组小母牛肺中eNOS的mRNA和蛋白水平高于HAPH组（均P<0.001），而HAPH组中内皮素-1蛋白水平高于健康组（P = 0.025）。补充NCG可降低mPAP和氨水平（均P = 0.001），而增加eNOS、精氨酸和血浆NO的表达（均P<0.05）。
患有HAPH的荷斯坦小母牛中eNOS的表达降低。补充NCG通过恢复eNOS和内源性NO合成降低了mPAP。
