Context: Although the primary cause of exercise-associated hyponatremia (EAH) is relative over-consumption of fluids beyond the kidneys ability to excrete excess fluid, the mechanisms limiting maximum renal excretory ability during exercise remain to be elucidated.

Objective: 1) Perform a comprehensive evaluation of the endocrine secretion of pituitary, natriuretic and adrenal steroid hormones, and cytokines, immediately before and after running an ultramarathon. 2) Evaluate the relationship between osmotic and non-osmotic stimuli to arginine vasopressin (AVP) secretion within the overall context of assessing the hormonal regulation of fluid balance during prolonged endurance exercise

Design: Observational study

Setting: 56 km ultramarathon

Participants: 82 runners

Interventions: none

Main Outcome Measures: Plasma sodium concentration ([Na⁺]), plasma volume, [AVP]_p

Results: Fluid homeostasis during exercise (356 ± 4 minutes) was maintained with ad libitum fluid intakes.[Na⁺] was maintained from pre-race (139.3 ± 0.3 mmol/L) to post-race (138.1 ± 0.4 mmol/L) with a significant decrease in plasma volume (-8.5 ± 0.1%, p<0.01). Increases in the plasma [AVP]_p, (3.9-fold), oxytocin (OT, 1.9-fold), brain natriuretic peptide (BNP, 4.5-fold) and interleukin-6 (IL-6, 12.5-fold) were highly significant (P<0.0001). Changes in BNP, OT and corticosterone were associated with 47% of the variance noted in [AVP]_p and 13% of the variance in plasma [Na⁺] in pathway analyses.

Conclusions:[AVP]_p was markedly elevated after the ultramarathon despite unchanged plasma [Na⁺]_. Therefore, an inability to maximally suppress [AVP] _P during exercise as a result of non-osmotic stimulation of AVP secretion may contribute to the pathogenesis of EAH if voluntary fluid intake were to exceed fluid output.