The Effect of Sodium Nitrite on Renal Function and Blood Pressure in Hypertensive Versus Healthy Subjects
- Registration Number
- NCT02527837
- Lead Sponsor
- Erling Bjerregaard Pedersen
- Brief Summary
The purpose of this study is to investigate how the effect of infused sodium nitrite differs in hypertensives compared to healthy age and sex matched controls. The effects on renal handling of nitrite, nitrate, sodium and water, plasma concentrations of vasoactive hormones, peripheral (brachial) and central blood pressure will be evaluated.
- Detailed Description
Nitric oxide (NO) is an important vasodilating molecule with a very complex biochemistry and metabolism. NO is classically synthesized from L-arginin by endothelial nitric oxide synthase (eNOS) located in the endothelial cell lining. Several chronic cardiovascular diseases such as hypertension, chronic kidney disease and diabetes are accompanied by endothelial dysfunction and hence diminished synthesis of NO. NO is a very reactive molecule and direct investigation of its function are limited and it has mainly been investigated by inhibition of eNOS. Recent research has shown that sodium nitrite is readily converted to NO by enzymes in vivo. The effects of sodium nitrite on renal variables, vasoactive hormones and central blood pressure are previously unexamined. It is now possible to achieve serial estimations of the central aortic systolic pressure (CASP) by a wrist born device.
Hypothesis:
1. Sodium nitrite infusion increases the urinary sodium excretion and glomerular filtration rate (GFR)
2. Sodium nitrite infusion increases plasma levels of nitrite, nitrate, NO and cyclic guanosine monophosphate (cGMP)
3. Sodium nitrite infusion lowers the peripheral and central blood pressure
4. Renal clearance of nitrite is constant and not dose dependent
5. Sodium nitrite infusion affects vasoactive hormones
6. The hemodynamic and renal effects is more pronounced in hypertensives as compared to healthy controls.
Purpose:
The purpose of this study is to investigate the effects of sodium nitrite infusion on
1. Renal handling of nitrite, nitrate, sodium and water
2. Plasma concentrations of vasoactive hormones
3. Peripheral (brachial) blood pressure and CASP
Design:
15 hypertensive subjects and 15 healthy, age and sex matched controls is recruited. Each subject will attend to two examination days. Four days prior to each examination day subjects are given a standardized diet with a low level of nitrate and nitrite. On the evening before the examination day the subjects take a single dose of lithium carbonate 300 mg in order to measure lithium clearance. On the examination days subjects are receiving a two hour infusion of either placebo (isotonic sodium chloride) or sodium nitrite. During the two examination days each subject receives both treatments in random order.
Perspectives:
Increasing knowledge about the nitrite-NO system can contribute to changing the clinical practise of diagnostics and treatment of cardiovascular diseases.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 30
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Sodium nitrite Sodium nitrite Sodium nitrite, 240 micrograms/kg/hour for 2 hours Placebo Sodium chloride Sodium chloride, isotonic 0.9%, 25 ml/hour for 2 hours
- Primary Outcome Measures
Name Time Method Fractional urinary sodium excretion (FENa) 1 day
- Secondary Outcome Measures
Name Time Method Peripheral (brachial) blood pressure 1 day Measured by oscillometric sphygmomanometer
Proximal sodium transport (Estimated by lithium clearance) 1 day Estimated by lithium clearance
Urinary excretion of cyclic guanosine monophosphate (cGMP) 1 day Urinary excretion of epithelial sodium channels (ENaC) 1 day Plasma concentration of angiotensin II (ANG2) 1 day Plasma concentration of aldosterone 1 day Plasma concentration of atrial natriuretic peptide (ANP) 1 day Plasma concentration of brain natriuretic peptide (BNP) 1 day Plasma concentration of cyclic guanosine monophosphate (cGMP) 1 day Plasma concentration of vasopressin (AVP, ADH) 1 day Glomerular filtration rate 1 day Urinary excretion of nitrite and nitrate (NOx) 1 day Free water clearance 1 day Plasma concentration of renin (PRC) 1 day Central aortic systolic blood pressure (CASP) 1 day Measured by tonometric pulse wave analysis. Device BPro from HealthSTATS international, Singapore
Plasma concentration of nitrite and nitrate (NOx) 1 day Urinary excretion of aquaporin 2 water channels (AQP2) 1 day Plasma concentration of endothelin 1 day
Trial Locations
- Locations (1)
Department of Medical Research and Medicine, Holstebro Regional Hospital
🇩🇰Holstebro, Denmark