Hamilton. Effects of high altitude and water deprivation on arginine vasopressin release in men. Am J Physiol Endocrinol Metab 286: E20-E24, 2004. First published September 3, 2003 10.1152/ ajpendo.00332.2003.-High-altitude exposure changes the distribution of body water and electrolytes. Arginine vasopressin (AVP) may influence these alterations. The purpose of this study was to examine the effect of a 24-h water deprivation trial (WDT) on AVP release after differing altitude exposures. Seven healthy males (age 22 Ϯ 1 yr, height 176 Ϯ 2 cm, mass 75.3 Ϯ 1.8 kg) completed three WDTs: at sea level (SL), after acute altitude exposure (2 days) to 4,300 m (AA), and after prolonged altitude exposure (20 days) to 4,300 m (PA). Body mass, standing and supine blood pressures, plasma osmolality (P osm), and plasma AVP (PAVP) were measured at 0, 12, 16, and 24 h of each WDT. Urine volume was measured at each void throughout testing. Baseline P osm increased from SL to altitude (SL 291.7 Ϯ 0.8 mosmol/kgH 2O, AA 299.6 Ϯ 2.2 mosmol/kgH2O, PA 302.3 Ϯ 1.5 mosmol/kgH 2O, P Ͻ 0.05); however, baseline PAVP measurements were similar. Despite similar P osm values, the maximal PAVP response during the WDT (at 16 h) was greater at altitude than at SL (SL 1.7 Ϯ 0.5 pg/ml, AA 6.4 Ϯ 0.7 pg/ml, PA 8.7 Ϯ 0.9 pg/ml, P Ͻ 0.05). In conclusion, hypoxia appeared to alter AVP regulation by raising the osmotic threshold and increasing AVP responsiveness above that threshold.acute mountain sickness; antidiuretic hormone; dehydration; fluid regulation; osmotic threshold EXPOSURE TO HIGH ALTITUDES may lead to acute mountain sickness (AMS), which is considered an indication of poor acclimatization. One distinct characteristic of AMS normally seen at altitude is the lack of a diuresis (10,11,26). Arginine vasopressin (AVP) has been implicated in AMS (4, 10) because of its role in reducing free water excretion at the kidney and because of altitude-induced increases in plasma osmolality (3-5), decreases in plasma volume (7,22,25), and increases in blood pressure (5, 21, 28), the three primary determinants of AVP release (23,27,29).Previous research examining the AVP response to altitude, however, does not support a role for AVP in AMS, because different exposures (1,900-5,400 m) of varying durations (3-30 days) have shown no rise in plasma AVP (P AVP ) (16,18,22). The lack of a P AVP response is paradoxical when we consider that altitude significantly alters plasma osmolality (P osm ) (3-5). Only one study has shown an augmentation in P AVP (24), this in response to 7 days of exposure to 4,200 m. Ramirez and colleagues (17, 19), however, have shown that high-altitude natives (2,600 m) have greater resting P AVP than sea-level natives.Osmotic challenges to evaluate the AVP response at altitude normally take the form of salt infusion. Typical results have shown similar increases in P osm with no change in P AVP between altitude and sea level infusions (17,18,20). Bestle et al. (3) showed that 8 days of exposure to 4,559 m enhanced baseline P osm and decr...