{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T18:50:38Z","timestamp":1777661438415,"version":"3.51.4"},"reference-count":62,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2024,9,1]],"date-time":"2024-09-01T00:00:00Z","timestamp":1725148800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["High Altitude Medicine &amp; Biology"],"published-print":{"date-parts":[[2024,9,1]]},"abstract":"<jats:p>\n                    Xiaoying Zhou, Wenting Su, Quanwei Bao, Yu Cui, Xiaoxu Li, Yidong Yang, Chengzhong Yang, Chengyuan Wang, Li Jiao, Dewei Chen, and Jian Huang. Nitric oxide ameliorates the effects of hypoxia in mice by regulating oxygen transport by hemoglobin.\n                    <jats:italic toggle=\"yes\">High Alt Med Biol<\/jats:italic>\n                    . 25:174\u2013185, 2024.\u2014Hypoxia is a common pathological and physiological phenomenon in ischemia, cancer, and strenuous exercise. Nitric oxide (NO) acts as an endothelium-derived relaxing factor in hypoxic vasodilation and serves as an allosteric regulator of hemoglobin (Hb). However, the ultimate effects of NO on the hematological system\n                    <jats:italic toggle=\"yes\">in\u00a0vivo<\/jats:italic>\n                    remain unknown, especially in extreme environmental hypoxia. Whether NO regulation of the structure of Hb improves oxygen transport remains unclear. Hence, we examined whether NO altered the oxygen affinity of Hb (Hb-O\n                    <jats:sub>2<\/jats:sub>\n                    affinity) to protect extremely hypoxic mice. Mice were exposed to severe hypoxia with various concentrations of NO, and the survival time, exercise capacity, and other physical indexes were recorded. The survival time was prolonged in the 5 ppm NO (6.09 \u00b1 1.29 minutes) and 10 ppm NO (6.39 \u00b1 1.58 minutes) groups compared with the 0 ppm group (4.98 \u00b1 1.23 minutes). Hypoxia of the brain was relieved, and the exercise exhaustion time was prolonged when mice inhaled 20 ppm NO (24.70 \u00b1 6.87 minutes vs. 20.23 \u00b1 6.51 minutes). In addition, the differences in arterial oxygen saturation (SO\n                    <jats:sub>2<\/jats:sub>\n                    %) (49.64 \u00b1 7.29% vs. 42.90 \u00b1 4.30%) and arteriovenous SO\n                    <jats:sub>2<\/jats:sub>\n                    % difference (25.14 \u00b1 8.95% vs. 18.10 \u00b1 6.90%) obviously increased. In\n                    <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                    experiments, the oxygen equilibrium curve (OEC) left shifted as P50 decreased from 43.77 \u00b1 2.49 mmHg (0 ppm NO) to 40.97 \u00b1 1.40 mmHg (100 ppm NO) and 38.36 \u00b1 2.78 mmHg (200 ppm NO). Furthermore, the Bohr effect of Hb was enhanced by the introduction of 200 ppm NO (\u22120.72 \u00b1 0.062 vs.\u22120.65 \u00b1 0.051), possibly allowing Hb to more easily offload oxygen in tissue at lower pH. The crystal structure reveals a greater distance between Asp94\u03b2-His146\u03b2 in nitrosyl -Hb(NO-Hb), NO-Hb\u03b2CSO93, and S-NitrosoHb(SNO-Hb) compared to tense Hb(T-Hb, 3.7 \u00c5, 4.3 \u00c5, and 5.8 \u00c5 respectively, versus 3.5 \u00c5 for T-Hb). Moreover, hydrogen bonds were less likely to form, representing a key limitation of relaxed Hb (R-Hb). Upon NO interaction with Hb, hydrogen bonds and salt bridges were less favored, facilitating relaxation. We speculated that NO ameliorated the effects of hypoxia in mice by promoting erythrocyte oxygen loading in the lung and offloading in tissues.\n                  <\/jats:p>","DOI":"10.1089\/ham.2023.0044","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T13:14:40Z","timestamp":1715692480000},"page":"174-185","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Nitric Oxide Ameliorates the Effects of Hypoxia in Mice by Regulating Oxygen Transport by Hemoglobin"],"prefix":"10.1177","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6993-2869","authenticated-orcid":false,"given":"Xiaoying","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of High Altitude Physiology and Pathology, College of High Altitude Military Medicine, Army Medical University, Chongqing, China."},{"name":"High Altitude Medical Research Center, PLA, Chongqing, China."},{"name":"Key Laboratory of High Altitude and Frigidzone Medical Surpport, PLA, Chongqing, China."},{"name":"Key Laboratory of Extreme Environmental Medicine, Ministry of Education, Chongqing, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenting","family":"Su","sequence":"additional","affiliation":[{"name":"Department of High Altitude Physiology and Pathology, College of High Altitude Military Medicine, Army Medical University, Chongqing, China."},{"name":"High Altitude Medical Research Center, PLA, Chongqing, China."},{"name":"Key Laboratory of High Altitude and Frigidzone Medical Surpport, PLA, Chongqing, China."},{"name":"Key Laboratory of Extreme Environmental Medicine, Ministry of Education, Chongqing, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quanwei","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Xinqiao Hospital, Army Medical University, Chongqing, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of High Altitude Physiology and Pathology, College of High Altitude Military Medicine, Army Medical University, Chongqing, China."},{"name":"High Altitude Medical Research Center, PLA, Chongqing, China."},{"name":"Key Laboratory of High Altitude and Frigidzone Medical Surpport, PLA, Chongqing, China."},{"name":"Key Laboratory of Extreme Environmental Medicine, Ministry of Education, Chongqing, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoxu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of High Altitude Physiology and Pathology, College of High Altitude Military Medicine, Army Medical University, Chongqing, China."},{"name":"High Altitude Medical Research Center, PLA, Chongqing, China."},{"name":"Key Laboratory of High Altitude and Frigidzone Medical Surpport, PLA, Chongqing, China."},{"name":"Key Laboratory of Extreme Environmental Medicine, Ministry of Education, Chongqing, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yidong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of High Altitude Physiology and Pathology, College of High Altitude Military Medicine, Army Medical University, Chongqing, China."},{"name":"High Altitude Medical Research Center, PLA, Chongqing, China."},{"name":"Key Laboratory of High Altitude and Frigidzone Medical Surpport, PLA, Chongqing, China."},{"name":"Key Laboratory of Extreme Environmental Medicine, Ministry of Education, Chongqing, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengzhong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of High Altitude Physiology and Pathology, College of High Altitude Military Medicine, Army Medical University, Chongqing, China."},{"name":"High Altitude Medical Research Center, PLA, Chongqing, China."},{"name":"Key Laboratory of High Altitude and Frigidzone Medical Surpport, PLA, Chongqing, China."},{"name":"Key Laboratory of Extreme Environmental Medicine, Ministry of Education, Chongqing, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of High Altitude Physiology and Pathology, College of High Altitude Military Medicine, Army Medical University, Chongqing, China."},{"name":"High Altitude Medical Research Center, PLA, Chongqing, China."},{"name":"Key Laboratory of High Altitude and Frigidzone Medical Surpport, PLA, Chongqing, China."},{"name":"Key Laboratory of Extreme Environmental Medicine, Ministry of Education, Chongqing, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of High Altitude Physiology and Pathology, College of High Altitude Military Medicine, Army Medical University, Chongqing, China."},{"name":"High Altitude Medical Research Center, PLA, Chongqing, China."},{"name":"Key Laboratory of High Altitude and Frigidzone Medical Surpport, PLA, Chongqing, China."},{"name":"Key Laboratory of Extreme Environmental Medicine, Ministry of Education, Chongqing, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dewei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of High Altitude Physiology and Pathology, College of High Altitude Military Medicine, Army Medical University, Chongqing, China."},{"name":"High Altitude Medical Research Center, PLA, Chongqing, China."},{"name":"Key Laboratory of High Altitude and Frigidzone Medical Surpport, PLA, Chongqing, China."},{"name":"Key Laboratory of Extreme Environmental Medicine, Ministry of Education, Chongqing, 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