Osmotic and nonosmotic regulation of arginine vasopressin during prolonged endurance exercise

J Clin Endocrinol Metab. 2008 Jun;93(6):2072-8. doi: 10.1210/jc.2007-2336. Epub 2008 Mar 18.


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

Objective: The objective of the study was to: 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; and 2) evaluate the relationship between osmotic and nonosmotic stimuli to arginine vasopressin (AVP) secretion within the overall context of assessing the hormonal regulation of fluid balance during prolonged endurance exercise.

Design: This was an observational study.

Setting: The study setting was a 56-km ultramarathon.

Participants: Eighty-two runners participated in the study.

Interventions: There were no interventions.

Main outcome measures: Plasma sodium concentration [Na(+)] and plasma volume [(AVP)(p)] were measured.

Results: Fluid homeostasis during exercise (356 +/- 4 min) was maintained with ad libitum fluid intakes. [Na(+)] was maintained from before the race (139.3 +/- 0.3 mmol/liter) to after the race (138.1 +/- 0.4 mmol/liter) with a significant decrease in plasma volume (-8.5 +/- 0.1%, P < 0.01). Increases in the plasma (AVP)(p) (3.9-fold), oxytocin (1.9-fold), brain natriuretic peptide (4.5-fold), and IL-6 (12.5-fold) were highly significant (P < 0.0001). Changes in brain natriuretic peptide, oxytocin, 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 nonosmotic stimulation of AVP secretion may contribute to the pathogenesis of exercise-associated hyponatremia if voluntary fluid intake were to exceed fluid output.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginine Vasopressin / blood
  • Arginine Vasopressin / metabolism
  • Arginine Vasopressin / pharmacokinetics*
  • Body Weight
  • Exercise / physiology*
  • Female
  • Hormones / blood
  • Humans
  • Hyponatremia / blood
  • Hyponatremia / etiology
  • Male
  • Models, Biological
  • Osmosis
  • Oxytocin / blood
  • Physical Endurance / physiology*
  • Time Factors
  • Water-Electrolyte Balance / physiology*


  • Hormones
  • Arginine Vasopressin
  • Oxytocin