Acute and chronic pulmonary pressor responses to hypoxia: the role of blunting in acclimatization.
We studied two strains of Sprague-Dawley rats: the Madison (M) that acclimatizes successfully to high altitude; and the Hilltop (H), that manifests signs of chronic mountain sickness at high altitude and has a high mortality rate. Awake, chronically instrumented animals were tested at sea level, at intervals during 30 days at a simulated altitude of 5500 m, and during 10 to 15 days of recovery at sea level. Mean pulmonary artery pressure (PAP) rose at high altitude to reach 60 mm Hg in H and 40 mm Hg in M, but the acute pressor response to hypoxia at sea level was much more pronounced in M than H. Depression of PAP by normoxic exposures in H rats at high altitude was slightly early in the period of stay but was enhanced with further prolongation of high altitude residence. The M rats, in contrast, had a blunted response (normoxia had very little depressant effect on PAP) after the first 24 h at high altitude, and it remained so for the duration of the stay. On return to sea level the response of H rats remained unchanged for 7 days, but the blunted response of the M rats at high altitude reversed at sea level to become exaggerated. We conclude: that responses of PAP to acute hypoxia do not forecast what the chronic response will be; that the appearance of an unidentified mechanism during chronic hypoxia in the M strain attenuates the vasoreactivity of the pulmonary vessels to hypoxia; and that the absence of such a blunting mechanism in H leads to the higher PAP in this strain and its morbid consequences. The hypothesis is put forward that the existence of such a blunting mechanism is an important factor in the adaptability of species to high altitude.
L C
LC
Ou
G L
GL
Sardella
N S
NS
Hill
S M
SM
Tenney
D000222:Adaptation, Physiological; D000531:Altitude; D000532:Altitude Sickness / Q000235:genetics / Q000503:physiopathology; D000818:Animals; D001794:Blood Pressure; D002908:Chronic Disease; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D000860:Hypoxia / Q000097:blood / Q000503:physiopathology*; D008297:Male; D011651:Pulmonary Artery / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains