The Role of Vasopressin Antagonism on Renal Sodium Handling
The Role of Vasopressin Antagonism on Renal Sodium Handling
Vasopressin has primarily been considered to be a water and osmosis regulating hormone that
 mediates its effects on renal aquaporin channels. Recent data suggest that vasopressin,
 through its V2 receptor, may also modulate sodium homeostasis. The purpose of this human
 physiology study was to test whether antagonism of the V2R alters urine sodium excretion in
 normal healthy volunteers.
Vasopressin's potential roles in maintaining normal volume homeostasis are expanding. While
 previous data support the concept that vasopressin's primary role is in mediating water
 homeostasis, recent data suggest that vasopressin, through its V2 receptor, may also modulate
 sodium homeostasis. This effect occurs via activation of the epithelial sodium channel
 (ENaC). These studies document that vasopressin via activation of the V2 receptor, not only
 reduces free water excretion but also sodium excretion. These data suggest that blocking this
 receptor under the right circumstances and in the right population may be effective in
 modulating hypertension in humans: specifically a V2 receptor antagonist may be effective in
 treating some individuals that have salt-sensitive hypertension. The current proposal will
 test in normal human subjects the proof of principle of the above stated hypothesis, and to
 assess the best markers to determine such an effect. It is important to perform studies with
 strict environmental control in a clinical research center because of the variability of
 environmental factors that can create confusion in interpreting data (dietary sodium,
 activity, body posture, diurnal variation, ambient temperature, sleep-wake cycle, etc.).

 The overall program objective is to determine if a vasopressin V2 antagonist will be an
 effective treatment for salt-sensitive hypertension and if so, what subtype. The object of
 this specific proposal is to determine the effect of a selective V2 antagonist on sodium
 handling in normal subjects.
Inclusion Criteria:

 -  - Blood pressure <130/85 mmHg and >100/50 mmHg

 -  Normal laboratory values for (see "Normal Values" table):

 -  Complete blood count

 -  Serum creatinine, sodium, potassium, glucose, liver enzymes

 -  Urinalysis

 -  ECG

 Exclusion Criteria:

 -  - Alcohol intake >12 oz per week

 -  Tobacco or recreational drug use

 -  History of coronary disease, diabetes, hypertension, stroke, kidney disease, or
 illness requiring overnight hospitalization in the past 6 months

 -  Any prescription medication or herbal medication use except oral contraceptive or
 multivitamin

 -  Pregnancy or current breastfeeding

 -  First degree relative with hypertension, diabetes, stroke, renal or cardiac disease