Hew-Butler T, Hummel J, Rider BC, Verbalis JG. Characterization of the effects of the vasopressin V2 receptor on sweating, fluid balance, and performance during exercise. Am J Physiol Regul Integr Comp Physiol 307: R366 -R375, 2014. First published June 18, 2014 doi:10.1152/ajpregu.00120.2014.-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 Ͻ2% across all three trials. Significant pharmacological condition effects were noted for urine osmolality [F ϭ 84.98; P Ͻ 0.0001] and urine sodium concentration ([Na ϩ ]) [F ϭ 38.9; P Ͻ 0.0001], which verified both pharmacological activation and inhibition of the V2R at the kidney collecting duct. Plasma osmolality and [Na ϩ ] demonstrated significant exercise (F ϭ 26.0 and F ϭ 11.1; P Ͻ 0.0001) and condition (F ϭ 5.1 and F ϭ 3.8; P Ͻ 0.05) effects (osmolality and [Na ϩ ], respectively). No significant exercise or condition effects were noted for either sweat or salivary [Na ϩ ]. Significant exercise effects were noted for plasma [AVP] (F ϭ 22.3; P Ͻ 0.0001), peak core temperature (F ϭ 103.3; P Ͻ 0.0001), percent body weight change (F ϭ 6.3; P ϭ 0.02), plasma volume change (F ϭ 21.8; P Ͻ 0.0001), and thirst rating (F ϭ 78.2; P Ͻ 0.0001). Performance time was not altered between conditions (P ϭ 0.80). In summary, AVP acting at V2R does not appear to regulate water losses from body fluids other than renal excretion during exercise. arginine vasopressin; sweat sodium; V2 antagonist; running ARGININE VASOPRESSIN (AVP) is the primary neuroendocrine regulator of water metabolism, acting to maintain plasma osmolality within the normal physiological range of 275-295 mosmol/kg H 2 O (38). Osmotic regulation of plasma tonicity generally occurs through activation of the vasopressin type 2 receptor (V2R) in the kidney. Activation of V2R initiates the translocation and subsequent insertion of aquaporin-2 (AQP2) water channels into the apical membrane of the collecting duct principal cells. This allows for water reabsorption along osmotic gradients and concomitant antidiuresis when plasma tonicities are high (46).Unlike this well-characterized interaction of V2R-stimulated translocation of AQP2 channels in the kidney, a regulatory effect of ...