Effect of the Known Antihypertensive Drug Telmisartan on Red Blood Cells and Circulation in the Smallest Blood Vessels

Influence of the Angiotensin Receptor Blocker Telmisartan on the Red Blood Cell Function and the Microcirculatory Perfusion

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.

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.

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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