Hematological and vasodilator characteristics for high altitude acclimatization in 2 Holstein heifers ascended to high altitude 3

Objective
This study was conducted to investigate hematological and vasodilator characteristics for high altitude acclimatization in Holstein heifers ascended to high altitude.


Methods
Holstein heifers resided at low altitude (LH; Beijing, China 43 meter), and Holstein heifers ascended to high altitude (Lhasa city, Tibet; 3,658 meter) after one year exposure including hypoxia acclimated Holstein heifers (AH; with mean pulmonary arterial pressure mPAP < 41 mmHg) and Holstein heifers affected by high altitude pulmonary hypertension (HAPH; with mPAP > 49 mmHg) and crossbred cattle (CB; Holstein × Tibet cattle) born and resided in Tibet were selected to compare parameters of blood gas, blood cells and vasodilators. Each group included 15 animals with 16 to 18 month of age.


Results
The HAPH had greater mPAP than other cattle classes (P < 0.01). Alveolar ventilation (as indicated by partial pressure of carbon dioxide; PaCO2) was improved in AH and HAPH compared to LH, but it was lower in HAPH than in CB and AH (P < 0.05). In addition, LH had the greatest and HAPH had the lowest partial pressure of oxygen (PaO2) among the four cattle classes (P < 0.05). Erythropoietin and mean corpuscular hemoglobin concentration were greater in AH and HAPH than LH (P < 0.05). Serum iron was greater in AH than LA and HAPH (P < 0.05). Hypoxia exposure increased plasma nitric oxide and endothelin-1 in cattle resided in Tibet compared to LH. Additionally, AH had greater brain natriuretic peptides than HAPH and LH, and AH had greatest C-type natriuretic peptides than the other groups (P < 0.05).


Conclusion
High altitude hypoxia acclimatization was achieved in Holstein heifers ascended to high altitude via augmented alveolar ventilation, serum iron, mean corpuscular hemoglobin concentration, natriuretic peptides and nitric oxide, it enables them to tolerate the high altitude.

High altitude hypoxic environment presents extreme challenges for cows because they have a small lung 49 volume relative to oxygen consumption [1,2]. Holstein and Angus cattle at high altitude were found to have 50 high prevalence of brisket disease (BD) [3,4] that imposes huge financial losses to farmers. On the contrary, 51 high altitude native breeds such as domestic Yaks (Bos grunniens) and Tibet cattle (Bos taurus) have genetic 52 phenotypical and physiological adaptations such as greater red blood cell (RBC) count, hemoglobin (HGB) 53 content, and hematocrit (HCT), and have lower prevalence of BD [5][6][7]. In Tibet, the offspring of Tibet cattle × 54 Holstein (frozen semen) were widely resided because they inherited high milk production of Holstein cattle and 55 high altitude genetic adaptation features of Tibet cattle.

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In human, acclimatization is found in people temporarily exposed to high altitude, which to some extent 57 allows them to tolerate the hypoxia by improving oxygen delivery capacity, but adaptation is the process of 58 natural acclimatization where genetical variations and acclimatization allow subjects to live without any 59 difficulties at high altitudes [8]

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Two mL blood sample were taken from the Jugular vein of each cow and transferred to a 3-mL tube 117 containing dipotassium-EDTA (1.8 g/L blood) to analyze blood cell parameters using a SYSMEX (xt4000i;

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Sysmex, Kobe, Japan). Another blood sample (3 mL) were collected from the jugular vein and allowed to clot 119 and serum was harvested and used for biochemical analyses. One mL coccygeal artery blood from each heifer 120 was collected in a tube containing 0.25 mL lithium heparin (1,000 IU/mL) to measure blood gas status using a 121 GEM premier 3000 (Instrumentation Laboratory, Orangeburg, NY) within one hour of sampling. and-inter-assay coefficients of variation were 7.7% (n = 15) and 11.5% (n = 15), respectively. Cross-reactivity 142 with BNP and atrial atriuretic peptide was less than 0.01%. Radioimmunoassay for pPlasma BNP concentrations Data are presented as Mean ± SEM. Data were tested for normality using a Kolmogorov-Smirnov test.

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Data were analyzed using one-way ANOVA followed by Tukey's multiple comparison test (Prism 5; Graph Pad hypoxemia to help them maintaining a normal blood oxygen content and arterial oxygen tension [29]

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and MCHC in CB was greater than HAPH (P < 0.05). The CB had the greatest (P < 0.05) serum iron followed 199 by AH, HAPH and LH. Holstein heifers at high altitude had greater (P < 0.05) HIF-1α than LH, but similar to 200 CB (P > 0.05;

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Hypoxia exposure increased NO expression, the CB, AH and HAPH had higher NO levels than LA (P < 226 0.05; Table 3). The eNOS was similar among the four classes (P > 0.05). The CB had greatest (P < 0.05) iNOS 227 among the four calsses of cattle, with LH and AH being intermitted and greater (P < 0.05) than HAPH. Hypoxia 228 exposure increased ET-1 levels, the CB, AH and HAPH had higher ET-1 than LH (P < 0.05), and ET-1 in AH 229 was greater (P < 0.05) than in CB. Low oxygen induces vasculature remodeling and constriction, lead to 230 pulmonary arterial hypertension which is modulated by a balance between vasoconstrictors (ET-1) and 231 vasodilators (NO). Augemented expression of NO contributed to the resistance to vasculature remodeling and 232 constriction that have been reported in Tibetans, Tibet sheep and Yaks [11,12,38]. In present study, cattle 233 A c c e p t e d A r t i c l e speculate that increased NO for Holstein heifers exposed to high altitude as a important adaption mechanism to 235 high-altitude hypoxia.