Role of Vascular Smooth Muscle in the Development of High Altitude Pulmonary Hypertension: An Interspecies Evaluation

Abstract

There is a marked variability in the degree of pulmonary hypertension induced by long-term exposure to altitudes above 3000 m among low altitude species, ranging from hyporesponders (sheep and dogs) to hyper-responders (cattle and pigs). The amount of inherent muscularization of small pulmonary arteries appears to be a determinant of this hypertensive response, as does the presence or absence of collateral ventilation. Hyper-responders also exhibit marked pulmonary vascular hypertrophy when exposed to long-term hypoxia. Humans exhibit similar inter- and intra-population variability. Animal species indigenous to high altitudes exhibit less variable, attenuated pulmonary hypertensive responses with little pulmonary vascular hypertrophy. This attenuated response is also apparent among human high altitude populations, particularly in Andean and Tibetan populations. Thus, successful adaptation to high altitudes is evident in species that do not sustain the acute cardiopulmonary compensations that occur upon initial exposure to high altitude.