Characterization of the effects of the vasopressin V2 receptor on sweating, fluid balance, and performance during exercise

Abstract

A regulatory effect of arginine vasopressin (AVP) on sweat water conservation has been hypothesized but not definitively evaluated. AVP-mediated insertion of sweat and salivary gland aquaporin-5 (AQP5) water channels through activation of the vasopressin type 2 receptor (V2R) remains an attractive, yet unexplored, mechanism that could result in a more concentrated sweat with resultant decreased water loss. Ten runners participated in a double-blind randomized control treadmill trial under three separate pharmacological conditions: a placebo, V2R agonist (0.2 mg desmopressin), or V2R antagonist (30 mg tolvaptan). After a familiarization trial, runners ran for 60 min at 60% of peak speed followed by a performance trial to volitional exhaustion. Outcome variables were collected at three exercise time points: baseline, after the steady-state run, and after the performance run. Body weight losses were <2% across all three trials. Significant pharmacological condition effects were noted for urine osmolality [F = 84.98; P < 0.0001] and urine sodium concentration ([Na(+)]) [F = 38.9; P < 0.0001], which verified both pharmacological activation and inhibition of the V2R at the kidney collecting duct. Plasma osmolality and [Na(+)] demonstrated significant exercise (F = 26.0 and F = 11.1; P < 0.0001) and condition (F = 5.1 and F = 3.8; P < 0.05) effects (osmolality and [Na(+)], respectively). No significant exercise or condition effects were noted for either sweat or salivary [Na(+)]. Significant exercise effects were noted for plasma [AVP] (F = 22.3; P < 0.0001), peak core temperature (F = 103.3; P < 0.0001), percent body weight change (F = 6.3; P = 0.02), plasma volume change (F = 21.8; P < 0.0001), and thirst rating (F = 78.2; P < 0.0001). Performance time was not altered between conditions (P = 0.80). In summary, AVP acting at V2R does not appear to regulate water losses from body fluids other than renal excretion during exercise.

Trial registration: ClinicalTrials.gov NCT02084797.

Keywords: V2 antagonist; arginine vasopressin; running; sweat sodium.

Fig. 1.

Diagrams of the double-blind, randomized control, study design (A) and randomized exercise laboratory protocol for trials 2, 3, and 4 (B).

Fig. 2.

Two-way repeated-measures ANOVA results for plasma and urine sodium ([Na⁺]) and potassium ([K⁺]) concentrations. Exercise is represented on the x-axis (Baseline, Steady-State, and Performance) and represents the temporal order in which the samples were taken. Condition (Placebo, V2R Agonist, and V2R Antagonist) is represented on the y-axis and represents the values obtained during each of the three separate pharmacological treatments. All data are represented by means (symbols) and standard deviation (bars). The standard deviation for the placebo trial (open circle) is represented by the wide “T” and solid line; the V2R Agonist trial (open square) is represented by the more narrow “T” and dashed line; while the V2R Antagonist (open triangle) is represented by the bold “I” and dotted line to distinguish between the overlapping error bars. Significant differences from post hoc analyses are represented on the graphs as follows: a, Significantly different from Placebo; b, significantly different from V2R agonist; and c, significantly different from V2R Antagonist.

Fig. 3.

Two-way repeated-measures ANOVA results for saliva and sweat sodium ([Na⁺]) and potassium ([K⁺]) concentrations. Exercise is represented on the x-axis (Baseline, Steady-State, and Performance) and represents the temporal order in which the samples were taken. Condition (Placebo, V2R Agonist, and V2R Antagonist) is represented on the y-axis and represents the values obtained during each of the three separate pharmacological treatments. All data are represented by means (symbols) and standard deviation (bars). The standard deviation for the placebo trial (open circle) is represented by the wide “T” and solid line; the V2R Agonist trial (open square) is represented by the more narrow “T” and dashed line; while the V2R Antagonist (open triangle) is represented by the bold “I” and dotted line to distinguish between the overlapping error bars. A statistically significant Exercise Effect was seen in saliva [Na⁺] (A) without a significant difference between conditions in post hoc analyses.

Fig. 4.

Two-way repeated-measures ANOVA results for plasma and urine osmolality, plasma arginie vasopressin (AVP) concentration ([AVP]_P) and plasma oxytocin concentration ([OT]_P). Exercise is represented on the x-axis (Baseline, Steady-State, and Performance) and represents the temporal order in which the samples were taken. Condition (Placebo, V2R Agonist, and V2R Antagonist) is represented on the y-axis and represents the values obtained during each of the three separate pharmacological treatments. All data are represented by means (symbols) and standard deviation (bars). The standard deviation for the placebo trial (open circle) is represented by the wide “T” and solid line; the V2R Agonist trial (open square) is represented by the more narrow “T” and dashed line; while the V2R Antagonist (open triangle) is represented by the bold “I” and dotted line to distinguish between the overlapping error bars. Significant differences from post hoc analyses are represented on the graphs as follows: a, Significantly different from Placebo; b, significantly different from V2R Agonist; and c, significantly different from V2R Antagonist.

Fig. 5.

Two-way repeated-measures ANOVA results for the change in sweat (A) and saliva [Na⁺] (B) from the placebo trial (V2R Agonist minus the placebo sodium concentration and V2R Antagonist minus the placebo sodium concentration) after both the steady-state and performance trial exercise time points.