The Effects of Nebivolol on the NO-system in Patients With Essential
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Fractional excretion of sodium
研究概览
简要总结
Investigators want investigate the following hypothesis:
- Nebivolol increases nitric oxide activity in the systemic circulation and the kidney
- The increased activity of nitric oxide during nebivolol treatment can be demonstrated by inhibition of NO synthesis with L-NMMA. We expect increased responses in blood pressure and sodium excretion is expected during nebivolol treatment compared to placebo.
详细描述
Beta-blockers are no longer recommended as first line treatment in essential hypertension. Evidence mainly based on clinical trails with the non-vasodilating beta-blockers atenolol and propanolol points towards that beta-blockers have an increased risk of stroke compared to ACE-inhibitors, calcium channel blockers and thiazides. However, this Nebivolol is a third generation beta-blocker with vasodilating properties. Nebivolol decreases peripheral blood pressure to the same extend as other beta-blockers but in contrast to atenolol nebivolol also reduces central blood pressure. Furthermore nebivolol increases nitric oxide (NO) availability in forearm vessels, maybe through activation of beta-3 receptors. The nitric oxide system plays a central role in both renal sodium and water handling and regulation of vascular tone and blood pressure. It has not been investigated if nebivolol changes NO availability in the kidney.
Investigators want investigate the following hypothesis:
- Nebivolol increases nitric oxide activity in the systemic circulation and the kidney
- The increased activity of nitric oxide during nebivolol treatment can be demonstrated by inhibition of NO synthesis with L-NMMA. Investigators expect increased responses in blood pressure and sodium excretion is expected during nebivolol treatment compared to placebo.
Purpose The purpose of this study is to investigate the effects of nebivolol on renal handling of sodium and water (Glomerular filtration rate, urine production, free water clearance, excretion of proteins from epithelial sodium channels (u-ENaCαβγ) and aquaporin channels (u-AQP2) and sodium and potassium excretion), plasma concentrations of vasoactive hormones (renin, angiotensin II, aldosterone, vasopressin, atrial natriuretic peptide, brain natriuretic peptide and endothelin), central blood pressure, pulse wave velocity (PWV) and augmentation index, under basal conditions and during inhibition of nitric oxide synthesis in patients with essential hypertension.
Design 25 patients with essential hypertension are recruited in this randomised, cross over, placebo-controlled, double blinded study with two treatment periods (nebivolol/placebo). Each subject will attend to two examination days. Four days prior to each examination days and on the morning of each examination day subjects are given either nebivolol 5 mg pr. day or placebo. During treatment periods subject are given a standardized diet. On the examination days subject are given L-NMMA, a nitric oxide synthase inhibitor, and renal function, central hemodynamic and vasoactive hormones are evaluated during basal conditions and during inhibition of nitric oxide synthesis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Increased blood pressure (above 135 mmHg systolic or 85 mmHg diastolic in day time in 24 hour blood pressure measurement taking 5 or 10 mg amlodipine
- •Men and women
- •age 40 - 70 years
- •informed consent
排除标准
- •diabetes mellitus
- •glomerular filtration rate < 30 ml/min
- •albuminuria > 1,5 g/l
- •renogram which suggests secondary hypertension
- •clinical signs of pheochromocytoma or increased p-metanephrines
- •clinical important sign og heart, lung, liver, thyroid or neoplastic diseases
- •clinical important deviations in routine blood samples or ECG
- •drug or alcohol abuse
- •pregnancy or nursery
- •intolerance to nebivolol
- •blood donation with a month of the first examination day
- •inacceptable increase in blood pressure durin L-NMMA infusion (200/120)
- •inacceptable side effects to amlodipine
- •blood pressure increase above 170/105 on highest dose amlodipine (10 mg)
研究组 & 干预措施
Nebivolol
Tablet Nebivolol 5 mg (oral use) for 5 days
干预措施: Nebivolol (Drug)
Placebo
Inactive placebo given as tablet for 5 days
干预措施: placebo (Drug)
结局指标
主要结局
Fractional excretion of sodium
时间窗: 5 days
次要结局
- Pulse wave velocity(5 days)
- Plasma renin concentration(5 days)
- Plasma brain natriuretic peptide concentration(5 days)
- Plasma vasopressin concentration(5 days)
- Glomerular filtration rate(5 days)
- Plasma Endothelin concentration(5 days)
- Urinary excretions of epithelial sodium channels(5 days)
- Urinary excretions of aquaprorin-2(5 days)
- 24-hour ambulatory blood pressure(5 days)
- Free water clearance(5 days)
- Urine flow(5 days)
- Blood pressure(5 days)
- Plasma aldosterone concentration(5 days)
- Plasma angiotensin II concentration(5 days)
研究者
Erling Bjerregaard Pedersen
MD
Regional Hospital Holstebro