Influence of the Angiotensin Receptor Blocker Telmisartan on the Red Blood Cell Function and the Microcirculatory Perfusion
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Changes in Elongation-Index (EI) Method: To determine the elongation index (EI) we use the Laser assisted optical rotational cell analyzer (Lorrca).
研究概览
简要总结
The hypothesis of the presented study is: Telmisartan induces an increase of eNOS activity in RBC resulting in an enhanced intravascular NO bioavailability, an ameliorated RBC deformability and a reduction of RBC and platelet aggregation. This could be a potential mechanism of the improvement of microcirculatory disorders, especially in patients with diabetes mellitus and arterial hypertension, treated with Telmisartan.
详细描述
Recently, it could be shown that the renin-angiotensin-system (RAS) influences different signal transduction pathways within the red blood cells (RBC). This includes the Na+/H+ exchange activity, the Ca2+-ATP-ase mediated Ca2+efflux, the erythropoietin- dependent production of RBC, the RBC deformability, RBC aggregation and the interaction of RBC and platelets. Recent studies and experiments, done by our group, focus on the oxidative and nitrosative metabolism of NO within the blood. The interactions of the RAS and endothelial NO are well known and described in detail. Based on a wide experience in this research field of NO metabolism, we characterized recently an active endothelial-type NO-synthase in RBC on the biochemical, functional and molecular level. Erythrocyte-derived NO formation serves important regulatory functions essential for adequate passage of blood through the vasculature. Here we aimed to treat patients with diabetes mellitus and arterial hypertension with Telmisartan as an angiotensin receptor antagonist. Efficacy parameters studied in this study should be: i) RBC deformability, RBC aggregation, ii) RBC dependent production of nitric oxide as well as detection of eNOS activity in RBC and iii) indices of microcirculatory perfusion. This project could broaden the view of effects of Telmisartan in the treatment of microcirculatory disorders in patients with diabetes mellitus and arterial hypertension, who exhibit a reduced NO bioavailability and RBC function.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Men older than 18 years
- •Diabetes mellitus type 2 defined according to the criteria of the American Diabetes Association Arterial hypertension defined according to the criteria of the Joint National Committtees (JNC 7)
- •Given informed consent
排除标准
- •Serve heart failure
- •Serve aortic valve stenosis or hypertrophy obstructive cardiomyopathy
- •Relevant cardiac arrhythmias
- •Acute myocardial infarction within the last 4 weeks
- •renal failure
- •bilateral renal artery stenosis
- •liver diseases
- •primary hyperaldosteronism
- •orthostatic hypotension (systolic blood pressure <100mmHg)
- •hypokalemia, hyponatremia, hypercalcemia, symptomatic hyperuricemia
- •inflammatory disease
- •malignant disease
- •previous intolerance to AT1 receptor antagonists and/or sulfonamides
- •current therapy with insulin sensitizer
- •current therapy with digoxin
- •known abuse of alcohol or drugs
研究组 & 干预措施
A
treatment with 80 mg Telmisartan per day for 30 days
干预措施: Telmisartan (Drug)
B
treatment with 20mg Telmisartan per day for 30 days
干预措施: Telmisartan (Drug)
结局指标
主要结局
Changes in Elongation-Index (EI) Method: To determine the elongation index (EI) we use the Laser assisted optical rotational cell analyzer (Lorrca).
时间窗: after 30 days of treatment with study drug/control
次要结局
- Improvement of microcirculatory perfusion (using laser doppler measurement)(after 30 days treatment)
- Improvement of endothelial function (using ultrasound measurements during flow mediated dilation)(after 30 days treatment)
- Increase in the total blood born NO pool (using reductive gase phase chemiluminescence(after 30 days treatment)
- Decrease of RBC aggregation (using Laser assisted optical rotational cell analyzer (Lorrca)(after 30 days of treatment)