The Effect of Sodium Nitrite on Renal Variables, Brachial and Central Blood Pressure in Healthy Humans. A Randomized, Cross Over, Placebo Controlled Dose-response Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Fractional urinary sodium excretion
研究概览
简要总结
The purpose of this study is to investigate the effect of different doses of sodium nitrite infusion in 12 healthy subjects. 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.
Hypothesis
Sodium nitrite infusion
- increases urinary sodium excretion and renal filtration rate
- lowers blood pressure, central as well as peripheral
- affects vasoactive hormones
- it is possible to establish a dose that affects the renal function with only minor effect on the blood pressure.
详细描述
Background:
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 newly designed wrist born device.
Hypothesis:
- Sodium nitrite infusion increases the urinary sodium excretion and glomerular filtration rate (GFR) in a dose related manner.
- Sodium nitrite infusion increases plasma levels of nitrite, nitrate, NO and cyclic guanosine monophosphate (cGMP)
- Sodium nitrite infusion lowers the peripheral and central blood pressure
- Renal clearance of nitrite is constant and not dose dependent
- Sodium nitrite infusion affects vasoactive hormones
- It is possible to establish a dose that affects the renal variables with only minor effect on the blood pressure.
Purpose:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •BMI 18,5-30 kg/m2
- •Women must use safe contraception
排除标准
- •Tobacco smoking, medicine or substance abuse
- •Weekly consumption of more than 21 standard drinks of alcohol for men and 14 standard drinks of alcohol for women (1 danish standard drink equals 12 grams of alcohol)
- •Medical treatment in the last 2 weeks except for contraception
- •Pregnancy or nursing
- •Diabetes mellitus
- •estimated glomerular filtration rate (eGFR) < 60 ml/min
- •clinically significant heart, lung, liver, kidney, metabolic og neurologic disease
- •clinically significant findings in screening blood samples, urine sample or ECG
- •Office blood pressure > 140/90 mmHg
- •Blood donation within 1 month of the first day of investigation
研究组 & 干预措施
40 micrograms sodium nitrite
Continuous 2 hour infusion of sodium nitrite, 40 micrograms/kg/hour
干预措施: Sodium nitrite, 40 micrograms/kg/hour (Drug)
120 micrograms sodium nitrite
Continuous 2 hour infusion of sodium nitrite, 120 micrograms/kg/hour
干预措施: Sodium nitrite, 120 micrograms/kg/hour (Drug)
240 micrograms sodium nitrite
Continuous 2 hour infusion of sodium nitrite, 240 micrograms/kg/hour
干预措施: Sodium nitrite, 240 micrograms/kg/hour (Drug)
Placebo
Continuous 2 hour infusion of sodium chloride, 25 ml/hour
干预措施: Placebo (Drug)
结局指标
主要结局
Fractional urinary sodium excretion
时间窗: One day
次要结局
- Nitrite clearance(One day)
- Nitrate clearance(One day)
- Glomerular filtration rate(One day)
- Proximal sodium transport(One day)
- Free water clearance(One day)
- Urinary excretion of cyclic guanosine monophosphate (cGMP)(One day)
- Urinary excretion of epithelial sodium channels (ENaC)(One day)
- Urinary excretion of water channels (aquaporin-2)(One day)
- Plasma concentration of renin(One day)
- Plasma concentration of aldosterone(One day)
- Plasma concentration of angiotensin 2(One day)
- Plasma concentration of atrial natriuretic peptide (ANP)(One day)
- Plasma concentration of brain natriuretic peptide (BNP)(One day)
- Plasma concentration of cyclic guanosine monophosphate (cGMP)(One day)
- Plasma concentration of endothelin(One day)
- Plasma concentration of vasopressin (AVP, ADH)(One day)
- Peripheral (brachial) blood pressure(One day)
- Central aortic systolic blood pressure (CASP)(One day)
研究者
Erling Bjerregaard Pedersen
Chief physician, PhD
Regional Hospital Holstebro