Blunted hypoxic pulmonary vasoconstrictive response in the rodentOchotona 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 Ppafrom 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-β 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.

Genomic analysis of snub-nosed monkeys (Rhinopithecus) identifies genes and processes related to high-altitude adaptation

“…4 and Supplementary npg l e t t e r s Note). These populations occupy different elevations at high altitude and may face different levels of hypoxia stress, similar to those experienced by other high-altitude mammals at comparable altitudes 27,28 . The high-altitude R. strykeri population was not included because of its small size, with fewer than 300 individuals in the wild, which led to sample collection difficulties.…”

VEGF189Expression Is Highly Related to Adaptation of the Plateau Pika (Ochotona curzoniae) Inhabiting High Altitudes

“…Native highaltitude animals have developed unique cardiovascular, hematological, and respiratory systems that ensure a successful adaptation to the harsh environment. Higher microvessel density, increased red blood corpuscle count, and blunted hypoxic pulmonary vasoconstriction response, which help animals to adapt to high-altitude hypoxia, have been reported in many plateau mammals (Anand et al, 1988, Anand et al, 1986, Azwai et al, 2007, Benavides et al, 1989, Durmowicz et al, 1993, Ge et al, 1998, Jiang et al, 1991, Jiang et al, 1992, Wei et al, 2006, Ye et al, 1994.…”

“…A number of strategies that are used by the pika to adapt to the harsh environment have been elucidated. These strategies include: 1) an increase in erythrocyte count, reduction in the mean corpuscular volume (Ye et al, 1994), changes in hemoglobin (Hb) and 2,3-diphosphoglycerate concentrations (Ge et al, 1998), and an increase in the oxygen affinity to Hb (He et al, 1994); 2) adaptation to its environment in terms of hepatic function, metabolism (Li et al, 1986), and neuroendocrine function (Du et al, 1983, Wu et al, 2001); 3) blunted hypoxic pulmonary vasoconstriction and thinwalled pulmonary arterioles (Ge et al, 1998); and 4) higher capillary densities, mitochondrial density, and concentration of myoglobin (for heart) in heart and lung . All these strategies reveal that the pika's adaptation to high altitudes occurs at both the physiological and biochemical levels.…”

The in-vivo oxyhaemoglobin dissociation curve at sea level and high altitude

“…Increased affinity has been achieved by changes in haemoglobin structure, as in deer mice in the Rocky Mountains (Storz et al, 2007) and high altitude chickens that were introduced to the Andes only 500 years ago (Velarde et al, 1991). Alternatively, it has also been achieved by a decrease in [2,, as in Tibetan pika (Ge et al, 1998), or by decreased influence of 2,3-DPG, as in bar-headed geese (Petschow et al, 1977).…”