Blunted hypoxic pulmonary vasoconstrictive response in the rodent Ochotona curzoniae (pika) at high altitude

Abstract

To investigate the possible mechanisms of adaptation to chronic hypoxia in the pulmonary circulation, we made direct measurements of pulmonary arterial pressure (Ppa) in 10 awake pika rodents that were transported to Xining, People's Republic of China (altitude 2,260 m) after being captured at 4,300 m and in 10 Wistar rats in a decompression chamber (simulated altitudes of 4,300 and 5,000 m) in Xining. Ppa was obtained at 1 h of exposure to each simulated altitude. The histology and immunohistochemistry of the lung tissues were also studied. Ppa in the pikas after the 4,300- and 5,000-m altitude exposures did not significantly increase, whereas in the rats Ppa rose significantly. Mean changes in Ppa from 2,260 to 4,300 and 5,000 m were 1.48 +/- 0.49 and 4.80 +/- 0.67 mmHg in the pikas and 10.38 +/- 3.36 and 19.10 +/- 2.28 mmHg in the rats. The ratio of right ventricular to left ventricular plus septal weight in the pikas and rats was 0.22 and 0.45, respectively. The pikas maintained levels of Hb, hematocrit, and 2,3-diphosphoglycerate lower than those of the rats. The percent wall thickness of the small pulmonary arteries in the pikas and rats was 9.22 and 27.21%, respectively, and it was well correlated with the degree of Ppa in both groups. Mast cells were observed in the lungs of the rats (7.1 +/- 0.33 cells/mm2) but not in the pikas. There was highly positive staining for mast cell tryptase and transforming growth factor-beta around pulmonary vessels in the rats, whereas no demonstrable reaction was observed in the pikas. We conclude that the pika has adapted to high altitude by losing hypoxic pulmonary vasoconstriction and thin-walled pulmonary arterioles.