Cardiovascular Diseases, Nephropathy
Conditions
Keywords
Tolvaptan, L-NMMA, Healthy subjects, Nephrology, Cardiology
Brief summary
The purpose of this study is to investigate the effect of tolvaptan on renal water, sodium and potassium excretion, plasma concentration of vasoactive hormones,central blood pressure, pulse wave velocity (PWV) and augmentation index, basal and during inhibition of nitric oxide synthesis in healthy subjects.
Detailed description
Tolvaptan is a vasopressin antagonist (V2-antagonist) and is used in treatment of hyponatremia. Animal studies have demonstrated that inhibition of V2 receptors in the renal principal cell increases renal free water clearance and renal sodium excretion. Treatment with V2-receptor antagonists increases vasopressin concentration in plasma that stimulates V1-receptors in the vascular bed. This may change both central and peripheral hemodynamics and plasma concentration of vasoactive hormones. Changes in hemodynamics and hormone concentration may consequently change renal sodium and water handling. The nitric oxide system plays a central role in both renal sodium and water handling and regulation of vascular tone and blood pressure. The effects of tolvaptan the circulation and kidneys is investigated by using measurements of biomarkers specific for the sodium/water balance in the urine and by measurements of vasoactive hormones in the blood after administration of tolvaptan and L-NMMA infusion.
Interventions
DRUGTolvaptan
15 mg pr day for 1 day
DRUGPlacebo
1 tablet Unikalk 1 pr day for 1 day
Sponsors
Regional Hospital Holstebro
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CH2O | 5-6 Hours | Measurement of H2O clearance at baseline, during and after L-NMMA infusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Central blood pressure | 5-6 Hours | — |
| Pulse wave velocity | 5-6 Hours | — |
| Urine biomarkers(Aquaporins, Epithelial Sodium Channels γ and β, Sodium/Chloride and Sodium/Potassium/Chloride cotransporter) | 5-6 Hours | — |
| Vasoactive Hormones( Angiotensin II, Aldosterone, Endothelin, Atrial Natriuretic Peptide, Brain Natriuretic Peptide, Arginin Vasopressin) | 5-6 Hours | — |
| Fractional sodium excretion | 5-6 Hours | Measurement of Sodium excretion at baseline, during and after L-NMMA infusion. |
| Augmentation Index | 5-6 Hours | — |
Countries
Denmark
Outcome results
None listed