The Role of Vasopressin Antagonism on Renal Sodium Handling

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