Potential genetic contributions to control of the pulmonary circulation and ventilation at high altitude.
This review examines evidence that genetic factors may be important determinants of response of the pulmonary circulation and ventilation at high altitude. Early observations of cattle at high altitude with brisket disease-pulmonary hypertension with right heart failure-found that the disorder ran in families. Subsequent studies confirmed a genetic determination of the pulmonary vasoconstrictor response to hypoxia by selective breeding of cattle for high and low responses. Clear interspecies and interstrain differences in the hypoxic pulmonary pressor response also underscore a major role for genetic influence in animals. In humans, differences in pulmonary hemodynamics are also evident among discrete populations living at altitude in the Andes, Himalayas, and North America suggesting an evolutionary, genetic influence on the response of the lung circulation to the hypoxia of altitude. Ventilation is increased by the hypoxia of high altitude. The strength of the ventilatory response to hypoxia shows considerable variation among individuals at low altitude. Family clusters of high and low responses and greater concordance among identical than fraternal twins suggest a strong genetic modulation of the human hypoxic ventilatory response. Similar effects are seen in interstrain differences among inbred strains of rats and mice. Differences among diverse altitude populations support the possible influence of genetic variation in the hypoxic response on ventilation and adaptation at altitude. Mechanisms linking genetic influences to variation in the hypoxic pulmonary pressor and ventilatory responses are unknown, but could reflect effects on hypoxic sensor, mediator or effector limbs of the response.
Fagan
K A
KA
Cardiovascular Pulmonary Research Laboratory, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver CO 80262, USA.
Weil
J V
JV
D000222:Adaptation, Physiological / Q000235:genetics*; D000531:Altitude; D000818:Animals; D002417:Cattle; D006801:Humans; D000860:Hypoxia / Q000235:genetics* / Q000503:physiopathology*; D051379:Mice; D011652:Pulmonary Circulation / Q000235:genetics*; D012123:Pulmonary Ventilation / Q000235:genetics*; D051381:Rats