Osmotic and nonosmotic regulation of arginine vasopressin during prolonged endurance exercise

Abstract

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.

Figure 1

Changes in adrenal steroid hormones from before to after the race within the pathway of steroid biosynthesis from cholesterol. The adrenal steroids measured in this study are noted inside each rectangular box. Mean differences (mean ± sem) between pre- and postrace concentrations are noted directly underneath each plasma steroid, respectively. The asterisks denote statistical significance from before to after the race. DHEA, Dehydroepiandrosterone; DHEAS, dehydroepiandrosterone sulfate; 17OH-pregnenolone, 17-hydroxypregnenolone; 17OH-progesterone, 17-hydroxyprogesterone.

Figure 2

Pathway diagram showing a significant mathematically predicted association of AVP Δ on plasma (Na⁺) Δ and corticosterone Δ on AVP Δ for the overall cohort (P < 0.05). Single and underlined values represent the entire cohort. Separate male (M) and female (F) coefficients are listed below the overall values. All reported values are standardized estimates, with unstandardized estimates in brackets. The double-headed arrows indicate the correlation estimates between the endogenous/independent variables. R² percent of the variation is explained by the direct antecedent(s).

Figure 3

Overall pathway diagram showing a significant mathematically predicted association of OT Δ on AVP Δ (P < 0.05) for the overall cohort. Separate male (M) and female (F) coefficients are listed below the overall values. All reported values are standardized estimates, with unstandardized estimates in brackets. R² percent of the variation is explained by the direct antecedent(s).

Figure 4

Pathway diagram for the female cohort only (n = 24) showing a significant mathematically predicted association of OT Δ on plasma (Na⁺) postrace values and AVP Δ (P < 0.05). All reported values are standardized estimates, with unstandardized estimates in brackets. R² percent of the variation is explained by the direct antecedent(s).

Figure 5

Linear relationships between AVP Δ with both plasma (Na⁺) Δ and OT Δ. The boxed area indicates a 20 mmol/liter range of plasma (Na⁺) Δ values associated with a corresponding 6 pg/ml (mean) change in (AVP)_P.