Effect of the Aquaretic Tolvaptan on Nitric Oxide System. A Dose-response Study (DOVA)

The Effects of Tolvaptan on Renal Handling of Water and Sodium, Vasoactive Hormones and Circulatory System, During Basal Conditions and During Inhibition of the Nitric Oxide System in Healthy Subjects. A Dose-response Study.

Tolvaptan is a selective vasopressin receptor antagonist (V2R) that increases free water and sodium excretion. Inhibition of V2R increases vasopressin concentration in plasma, which stimulates V1-receptors in the vascular bed and may change both central and brachial hemodynamics and plasma concentration of vasoactive hormones.

The purpose of the study is to measure the effects of tolvaptan on renal handling of water and sodium, systemic hemodynamics and vasoactive hormones at baseline and during nitric oxide (NO)-inhibition with L-NG-monomethyl-arginine (L-NMMA).

Inclusion Criteria:

• Men and women, age 18-40 years
• Body Mass Index (BMI) 18,5-30 kg/m2

Exclusion Criteria:

• Anamnestic or clinical signs of heart, lung, lever, kidney and brain disease
• Neoplastic disease
• Drug abuse
• Alcohol abuse
• Medical treatment except peroral anticontraceptive
• Pregnancy
• Smoking
• Abnormal blood and urine sample
• Abnormal ECG
• Blood donation within a month before examination
• Arterial hypertension (>140 mmHg systolic and/or 90 mmHg diastolic)