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| Name | Class |
|---|---|
| Herning Hospital | OTHER |
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Treatment with nitrate has shown to lower blood pressure in both healthy subjects and hypertensive patients.Beside this nitrate have also shown to decrease arterial stiffness and improve endothelial function.But the effect of nitrate on renal blood flow, kidney function, water and salt balance and vasoactive hormones is still unclear.
Therefore, the purpose of this study is to investigate the effect of orally administered nitrate on these parameters.
This will be done in a double-blinded, placebo-controlled, crossover study. 20 healthy subjects will be treated, in a randomized order, with both potassium nitrate and placebo separated by at least 4 weeks wash-out.
Inorganic nitrate reduces blood pressure and improves endothelial function in both healthy subjects and hypertensive patients.
This effect is thought to be caused through bioconversion to nitric oxide. Thus improving risk factors of cardiovascular decease by increasing vasodilatation, salt regulation and vasoactive hormones.The purpose of this study is to investigate the effect of inorganic nitrate on kidney function, hormones and circulation, which is still unknown.
The effect of 4 days treatment with 24 mmol potassium nitrate capsules on heart rate, blood pressure, vasoactive hormones and urinary excretion of sodium and water will be measured in a randomized, placebo controlled, double blinded, crossover study in 20 healthy subjects. Each subject attends 2x2 examination days at least 4 weeks apart. The examination days are divided into 8 clearance periods of 30 min. each. The first 3 are baseline periods and in period 4 1 Liter of saline is administered to detect any difference in renal parameters after NaCl load.
If inorganic nitrate supplementation is found to lower blood pressure in addition to favorable renal effects, it could lead to changes in the general treatment of high blood pressure and cardiovascular disease.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Potassium Nitrate | Active Comparator | 4 days treatment with 24 mmol potassium nitrate capsules |
|
| Potassium Chloride | Placebo Comparator | 4 days treatment 24 mmol potassium chloride capsules |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| isotonic saline 9% | Other | 1 Liter of Isotonic saline administered I.V. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Glomerular filtration rate (GFR) | mL/minute | analysed right after each examination day. (day 1) |
| Measure | Description | Time Frame |
|---|---|---|
| Brachial blood pressure (BP) | mmhg | analysed right after each examination day. (day 1) |
| central blood pressure (cSBP) | mmhg | analysed right after each examination day. (day 1) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jesper N Bech, Ph.D., M.D. | University of Aarhus | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Godstrup Hospital | Herning | 7400 | Denmark |
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| ID | Term |
|---|---|
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| C023844 | potassium nitrate |
| D011189 | Potassium Chloride |
| ID | Term |
|---|---|
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
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double-blinded, placebo-controlled, crossover study
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The Hospital Pharmacy, Herning Hospital, generates the randomization list. A copy of the list is kept at the Medical Research department.
Patients are randomized to receive either potassium nitrate or placebo (Potassium chloride). The Hospital Pharmacy, Gødstrup Hospital, will blind both treatments.
| Potassium nitrate | Dietary Supplement | 24 mmol of Potassium nitrate is the active comparator substance, that is ingested every morning for 4 days before and on the examination day. |
|
| Potassium chloride | Dietary Supplement | 24 mmol of Potassium nitrate is the placebo substance, that is ingested every morning for 4 days before and on the examination day. |
|
| Heart rate | beats pr. min. | analysed right after each examination day. (day 1) |
| Pulse wave velocity (PWV) | measured via Mobilograph | analysed right after each examination day. (day 1) |
| Total vascular resistance (TVR) | measured via Mobilograph | analysed right after each examination day. (day 1) |
| Augmentation index (Aix@75) | measured via Mobilograph | analysed right after each examination day. (day 1) |
| Urinary excretions of aquaporin-2 (u-AQP2) | ng/mmol crea | Centrifuged and hereafter frozen. Analyzed during the following 12 months. |
| Urinary excretions of epithelial sodium channels (u-ENaCγ) | ng/mmol crea | Centrifuged and hereafter frozen. Analyzed during the following 12 months. |
| Urinary excretions of Na-Cl cotransporter (u-NCC). | ng/mmol crea | Centrifuged and hereafter frozen. Analyzed during the following 12 months. |
| plasma concentration of renin (PRC) | pg/mL | Centrifuged and hereafter frozen. Analyzed during the following 12 months. |
| plasma concentration of angiotensin II (p-AngII) | pg/mL | Centrifuged and hereafter frozen. Analyzed during the following 12 months. |
| plasma concentration of aldosterone (p-Aldo) | pmol/L | Centrifuged and hereafter frozen. Analyzed during the following 12 months. |
| plasma concentration of arginine vasopressin (p-AVP) | pg/mL | Centrifuged and hereafter frozen. Analyzed during the following 12 months. |
| plasma concentration of atrial natriuretic peptide (p-ANP) | pmol/L | Centrifuged and hereafter frozen. Analyzed during the following 12 months. |
| plasma concentration of brain natriuretic peptide (p-BNP). | pmol/L | Centrifuged and hereafter frozen. Analyzed during the following 12 months. |
| plasma and urine levels of Nitrate (NO3) | μmol/L | Centrifuged and hereafter frozen. Analyzed during the following 12 months. |
| plasma and urine levels of nitrite (NO2) | μmol/L | Centrifuged and hereafter frozen. Analyzed during the following 12 months. |
| plasma and urine levels of cyclic guanosine monophosphate (cGMP). | pmol/mL | Centrifuged and hereafter frozen. Analyzed during the following 12 months. |
| Creatinine clearance (CrCl) | mL/minute | analysed right after each examination day. (day 1) |
| Urinary excretion rate of sodium (U-Na) | mmol/min | analysed right after each examination day. (day 1) |
| Urinary excretion rate of potassium(U-K) | mmol/min | analysed right after each examination day. (day 1) |
| Free water clearance (CH2O) | mL/minute | analysed right after each examination day. (day 1) |
| Fractional excretion of sodium (FENa) | calculated into % | analysed right after each examination day. (day 1) |
| Fractional excretion of potassium (FEK) | calculated into % | analysed right after each examination day. (day 1) |
| Urinary excretion rate of albumin (UAER) | µg/min | analysed right after each examination day. (day 1) |
| D017680 |
| Potassium Compounds |