The Effect of Orally Administrated Nitrate on Renal Parameters and Systemic Haemodynamics
- Conditions
- Hypertension
- Interventions
- Other: isotonic saline 9%Dietary Supplement: Potassium chlorideDietary Supplement: Potassium nitrate
- Registration Number
- NCT04755400
- Lead Sponsor
- Frank Mose
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 18
- Age 18-64 years
- BMI 18,5-30
- Normotensive
- Women must use contraception
- Tobacco smoking (Non-smokers in more than 3 months can be included)
- Medicine- or drug abuse
- Alcohol abuse >7 units for women >14 units for men
- Medical treatment (over the counter medication will evaluated whether or not it is grounds for exclusion) within 2 weeks before the trail period starts except contraception.
- Pregnancy or nursing
- Neoplastic disorders
- Significant clinical signs of heart-, lung-, liver-, kidney-, endocrine- or brain disorders
- Clinically significant abnormal findings in screening blood samples, urine sample or ECG - Donation of blood within 1 month of the first day of investigation.
- Allergy against compounds in investigational medicine
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Potassium Chloride isotonic saline 9% 4 days treatment 24 mmol potassium chloride capsules Potassium Chloride Potassium chloride 4 days treatment 24 mmol potassium chloride capsules Potassium Nitrate isotonic saline 9% 4 days treatment with 24 mmol potassium nitrate capsules Potassium Nitrate Potassium nitrate 4 days treatment with 24 mmol potassium nitrate capsules
- Primary Outcome Measures
Name Time Method Glomerular filtration rate (GFR) analysed right after each examination day. (day 1) mL/minute
- Secondary Outcome Measures
Name Time Method Urinary excretions of Na-Cl cotransporter (u-NCC). Centrifuged and hereafter frozen. Analyzed during the following 12 months. ng/mmol crea
Brachial blood pressure (BP) analysed right after each examination day. (day 1) mmhg
Urinary excretions of epithelial sodium channels (u-ENaCγ) Centrifuged and hereafter frozen. Analyzed during the following 12 months. ng/mmol crea
plasma concentration of angiotensin II (p-AngII) Centrifuged and hereafter frozen. Analyzed during the following 12 months. pg/mL
Urinary excretion rate of albumin (UAER) analysed right after each examination day. (day 1) µg/min
central blood pressure (cSBP) analysed right after each examination day. (day 1) mmhg
Pulse wave velocity (PWV) analysed right after each examination day. (day 1) measured via Mobilograph
plasma and urine levels of cyclic guanosine monophosphate (cGMP). Centrifuged and hereafter frozen. Analyzed during the following 12 months. pmol/mL
Total vascular resistance (TVR) analysed right after each examination day. (day 1) measured via Mobilograph
plasma concentration of renin (PRC) Centrifuged and hereafter frozen. Analyzed during the following 12 months. pg/mL
Creatinine clearance (CrCl) analysed right after each examination day. (day 1) mL/minute
Augmentation index (Aix@75) analysed right after each examination day. (day 1) measured via Mobilograph
Heart rate analysed right after each examination day. (day 1) beats pr. min.
Urinary excretions of aquaporin-2 (u-AQP2) Centrifuged and hereafter frozen. Analyzed during the following 12 months. ng/mmol crea
plasma concentration of arginine vasopressin (p-AVP) Centrifuged and hereafter frozen. Analyzed during the following 12 months. pg/mL
Urinary excretion rate of sodium (U-Na) analysed right after each examination day. (day 1) mmol/min
Fractional excretion of potassium (FEK) analysed right after each examination day. (day 1) calculated into %
plasma concentration of aldosterone (p-Aldo) Centrifuged and hereafter frozen. Analyzed during the following 12 months. pmol/L
plasma concentration of atrial natriuretic peptide (p-ANP) Centrifuged and hereafter frozen. Analyzed during the following 12 months. pmol/L
plasma concentration of brain natriuretic peptide (p-BNP). Centrifuged and hereafter frozen. Analyzed during the following 12 months. pmol/L
plasma and urine levels of Nitrate (NO3) Centrifuged and hereafter frozen. Analyzed during the following 12 months. μmol/L
Urinary excretion rate of potassium(U-K) analysed right after each examination day. (day 1) mmol/min
plasma and urine levels of nitrite (NO2) Centrifuged and hereafter frozen. Analyzed during the following 12 months. μmol/L
Free water clearance (CH2O) analysed right after each examination day. (day 1) mL/minute
Fractional excretion of sodium (FENa) analysed right after each examination day. (day 1) calculated into %
Trial Locations
- Locations (1)
Godstrup Hospital
🇩🇰Herning, Denmark