V2 Receptor Effects on Fluid Regulation and Performance

Not Applicable

Completed

Conditions: Hypernatremia
Electrolyte Imbalance
Hyponatremia

Interventions: Drug: V2R (Vasopressin 2 receptor)

Registration Number: NCT02084797

Lead Sponsor: Oakland University

Brief Summary: This primary aim of this study was to critically assess whether or not sweat water content and sodium concentration were acutely regulated by dynamic changes in antidiuretic hormone (arginine vasopressin or AVP) acting on the Vasopressin 2 receptor (V2R) during exercise. Secondary aims were to evaluate running performance and core temperature to further characterize the role of AVP in the coordinated balance of fluid and temperature homeostasis during exercise. The primary hypothesis was that activation of the V2R in sweat glands would result in water reabsorption and fluid conservation during endurance exercise.

Detailed Description: Ten healthy habitual runners (\> 50km running per week) between 18-60 years of age participated in this double blind randomized control trial. Each subject presented to the exercise lab on four separate occasions. Trial 1 was a familiarization trial to determine each subject's maximal aerobic capacity and peak treadmill running speak (VO2 Peak test). Trials 2, 3 and 4 utilized the same exact protocol, differing only in pharmacological intervention. In a randomized, double-blind order (both participant and investigator blinded to the intervention), either a placebo pill, the V2 receptor antagonist tolvaptan (Samsca™, 30mg tablet), or the V2 receptor agonist desmopressin (DDAVP™, 0.2mg tablet) was ingested along with the CorTemp™ Core Temperature Sensor two hours before commencement of the Exercise Trial with 240mL of bottled water. The exercise protocol consisted of 60 minutes of treadmill running at 60% of peak speed (steady-state) followed by a performance test (the VO2 Peak test). Blood, saliva and urine, were collected before the exercise trial (baseline) and again after both the steady-state run and performance runs. Sweat was obtained from sweat patches after both the steady-state and performance runs. Core temperature, fluid intake, performance time, body weight, thirst and sodium palatability ratings were also assessed. Free access to water was allowed during the trial and all urine produced during the trial was measured and collected. The main outcome measure was sweat sodium concentration.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 10

Inclusion Criteria

Healthy (no acute or chronic medical conditions or regular prescription medication use), habitual (>50km/week)
Distance runners between the ages of 18-60 years.

Exclusion Criteria

Individuals with chronic medical problems which require regular prescription medication
Runners with pre-existing kidney problems
Unable to sense thirst
Difficulty swallowing
Gastrointestinal disorders
History of fainting associated with blood draw.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
all study participants	V2R (Vasopressin 2 receptor)	All study participants received all interventions. V2R Antagonist: 30mg Tolvaptan tablet ingested 2 hours before exercise. V2R agonist: 0.2mg DDAVP tablet ingested 2 hours before exercise Placebo

Primary Outcome Measures

Name	Time	Method
Sweat Sodium Concentration Obtained After the Steady-state Portion of the Trial	4 study trials (4 weeks)	Changes in sweat sodium concentration will parallel changes in urine sodium concentration with use of the V2R antagonist, agonist and placebo if the primary hypothesis is true (sweat sodium is regulated by the V2R, similar to how urine sodium is regulated by principle cells located within in the kidney collecting duct)

Secondary Outcome Measures

Name	Time	Method
Urine Sodium Concentration After the Steady-state Portion of the Trial	4 study trials (4 weeks)	Changes in urine sodium concentration after use of the V2R antagonist, agonist and placebo interventions will verify whether or not pharmacologic activation or inhibition was successfully induced.
Blood Sodium Concentration	4 study trials (4 weeks)	Measurement of blood sodium concentration will determine if normonatremia (blood sodium concentrations within the normal physiological range of 135-145mmol/L) were maintained throughout the trial with appropriate fluid intake during the V2R antagonist, agonist and placebo intervention trials.
Saliva Sodium Concentration	4 trials (4 weeks)	Measurement of salivary sodium concentration will allow us to determine if the V2R antagonist, agonist and placebo interventions activate aquaporin-5 (AQP5) water channels that are also located in sweat glands. If the V2R acts on the sweat glands through AQP5, there should be parallel changes in sweat, urine and saliva sodium concentrations with each pharmaceutical intervention.