Arginine Vasopressin, Fluid Balance and Exercise

The ability of the human body to regulate plasma osmolality (POsm) within a very narrow and well defined physiological range underscores the vital importance of preserving water and sodium balance at rest and during exercise. The principle endocrine regulator of whole body fluid homeostasis is the posterior pituitary hormone, arginine vasopressin (AVP). Inappropriate AVP secretion may perpetuate either slow or rapid violation of these biological boundaries, thereby promoting pathophysiology, morbidity and occasional mortality. In the resting state, AVP secretion is primarily regulated by changes in POsm (osmotic regulation). The osmotic regulation of AVP secretion during exercise, however, may possibly be enhanced or overridden by many potential non-osmotic factors concurrently stimulated during physical activity, particularly during competition. The prevalence of these highly volatile non-osmotic AVP stimuli during strenuous or prolonged physical activity may reflect a teleological mechanism to promote water conservation during exercise. However, non-osmotic AVP secretion, combined with high fluid availability plus sustained fluid intake (exceeding fluid output), has been hypothesized to lead to an increase in both the incidence and related deaths from exercise-associated hyponatraemia (EAH) in lay and military populations. Inappropriately, high plasma AVP concentrations ([AVP]_p) associated with low blood sodium concentrations facilitate fluid retention and sodium loss, thereby possibly reconciling both the water intoxication and sodium loss theories of hyponatraemia that are currently under debate. Therefore, given the potential for a variety of exercise-induced non-osmotic stimuli for AVP secretion, hydration strategies must be flexible, individualized and open to change during competitive events to prevent the occurrence of rare, but life-threatening, EAH.

This review focuses on the potential osmotic and non-osmotic stimuli to AVP secretion that may affect fluid homeostasis during physical activity. Recent laboratory and field data support: (i) stimulatory effects of exercise intensity and duration on [AVP]_p; (ii) possible relationships between changes in POsm with changes in both sweat and urinary osmolality; (iii) alterations in the AVP osmoregulatory set-point by sex steroid hormones; (iv) differences in [AVP]_p in trained versus untrained athletes; and (v) potential inter-relationships between AVP and classical (aldosterone, atrial natriuretic peptide) and non-classical (oxytocin, interleukin-6) endocrine mediators. The review concludes with a hypothesis on how sustained fluid intakes beyond the capacity for fluid loss might possibly facilitate the development of hyponatraemia if exercise-induced non-osmotic stimuli override ‘normal’ osmotic suppression of AVP when hypo-osmolality exists.