BACKGROUND: The normal physiological response to high altitude (HA) is a decrease in total body water (TBW) and plasma and extracellular volume. The present investigation was designed to determine the mechanisms of the decrease in TBW with HA adaptation. METHOD: There were 10 men from the Southern Colombian Andes (2600 m) in Pasto, Colombia, who were compared to age-matched men from sea level (SL), Tampa, FL, in the U.S., with respect to their TBW, ability to handle a water load and response to exogenous arginine vasopressin (AVP). Measurements included circulating AVP, atrial natriuretic peptides [atrial natriuretic factor (ANF) and vessel dilator], and urinary excretion of the AVP sensitive water channel, aquaporin-2 (AQP2). RESULTS: The HA subjects had significantly (p < 0.01) lower TBW (29.37 +/- 0.98 vs 39.71 +/- 1.66 Kg), AQP2 excretion and vessel dilator circulating levels at baseline compared to SL subjects. ANF levels were not significantly different between the two groups. With water loading (20 ml.kg-1 in 15 min) there was a rapid increase in urine volume at 30 min with a decline thereafter in HA subjects while SL subjects had a gradual increment peaking at 120 min. There was a significant (p < 0.05) decrease in plasma AVP in the SL subjects within 30 min after the water load while the HA subjects had no significant decrease in AVP levels. Excretion of AQP2 decreased significantly after the water load only in the SL subjects. Administration of exogenous AVP increased AQP2 3- to 4-fold in the HA in comparison to SL subjects. CONCLUSIONS: Present data demonstrate the following adaptations to HA: decrease in TBW, better ability to handle a water load despite high levels of AVP, a significant decrease in the circulation of vessel dilator, and diminished excretion of AQP2 water channel. These findings indicate an insensitivity of the collecting duct of HA subjects to the actions AVP. However, exogenous administration of AVP caused a marked excretion of AQP2.
BACKGROUND: The normal physiological response to high altitude (HA) is a decrease in total body water (TBW) and plasma and extracellular volume. The present investigation was designed to determine the mechanisms of the decrease in TBW with HA adaptation. METHOD: There were 10 men from the Southern Colombian Andes (2600 m) in Pasto, Colombia, who were compared to age-matched men from sea level (SL), Tampa, FL, in the U.S., with respect to their TBW, ability to handle a water load and response to exogenous arginine vasopressin (AVP). Measurements included circulating AVP, atrial natriuretic peptides [atrial natriuretic factor (ANF) and vessel dilator], and urinary excretion of the AVP sensitive water channel, aquaporin-2 (AQP2). RESULTS: The HA subjects had significantly (p < 0.01) lower TBW (29.37 +/- 0.98 vs 39.71 +/- 1.66 Kg), AQP2 excretion and vessel dilator circulating levels at baseline compared to SL subjects. ANF levels were not significantly different between the two groups. With water loading (20 ml.kg-1 in 15 min) there was a rapid increase in urine volume at 30 min with a decline thereafter in HA subjects while SL subjects had a gradual increment peaking at 120 min. There was a significant (p < 0.05) decrease in plasma AVP in the SL subjects within 30 min after the water load while the HA subjects had no significant decrease in AVP levels. Excretion of AQP2 decreased significantly after the water load only in the SL subjects. Administration of exogenous AVP increased AQP2 3- to 4-fold in the HA in comparison to SL subjects. CONCLUSIONS: Present data demonstrate the following adaptations to HA: decrease in TBW, better ability to handle a water load despite high levels of AVP, a significant decrease in the circulation of vessel dilator, and diminished excretion of AQP2water channel. These findings indicate an insensitivity of the collecting duct of HA subjects to the actions AVP. However, exogenous administration of AVP caused a marked excretion of AQP2.