Does endurance training attenuate inflammatory response under chronic hypoxic adaptation?



Recently, altitude training has widely been accepted by elite athletes as an efficient way to improve endurance capacity. Most athletes and coaches who adopt altitude training aim to increase red blood cell volume, hematocrit or hemoglobin concentration caused by hypoxic response. Extreme hypoxic conditions, however, may lead to fatal acute mountain sickness. Acute inflammatory response is known to contribute to the development of pulmonary hypertension and edema in severe mountain sickness. Since HIFs induced by hypoxia are known to be responsible for not only erythrocytosis but also leukocytosis under low hypobaric hypoxia, we used a conditional knockout (cKO) mouse of proryl hydroxylase domain 2(PHD2) in which HIFs are constitutively activated. We tested whether exercise training of Phd2 cKO mouse may attenuate inflammatory response leading to reduction in the risk of pulmonary injury.


Because Phd2 knockout is embryonic lethal, estrogen receptor (ER) agonist induced Phd2 cKO mouse using Cre-loxP system was used. Three days after estrogen-agonist tamoxifen or vehicle administration, endurance test using a rodent treadmill was performed. Phd2 cKO mice and controlmice were then divided into two groups. The mice in the training group underwent 2-week interval training on a rodent treadmill. After 2 weeks all mice of both groups were tested again for their endurance capacity and were sacrificed for blood and tissue examination.


Phd2 cKO mice exhibited marked increase in hematocrit, hemoglobin concentration and RBC counts as well as increased WBC count with markedly enlarged spleen. Endurance time of trained mice of both of Phd2 cKO and control were significantly improved (Improve rate (%) in control and cKO group were 43.6±21.1 and 21.9 21.1, p=n.s.), but the improvement was not different between control and Phd2 cKO mice. The level of leukocytosis was not attenuated even after exercise training.


Exercise training, which improved endurance capacity, could not attenuate leukocytosis elicited by constitutive hypoxic response. In addition chronic hypoxic response, which may mimic altitude training, did not improve exercise capacity or the training effect.

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