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Markers of endothelial function in the early stages of essential hypertension and the effect of antihypertensive therapy


Authors: A. Remková 1;  M. Remko 2,1
Authors‘ workplace: Centrum hemostázy a trombózy, HemoMedika Bratislava s. r. o., Bratislava, Slovenská republika, odborný garant prof. MU Dr. Anna Remková, PhD., DrSc. 2 Farmaceutická fakulta UK Bratislava, Slovenská republika, dekan prof. PharmDr. Ján Kyselovič, PhD. 1
Published in: Vnitř Lék 2010; 56(12): 1210-1216
Category: Original Contributions

Overview

Objective:
Endothelial abnormalities appear to play a role in the pathogenesis of atherosclerotic/ atherothrombotic complications of hypertension. They may contribute to the increased risk and severity of target organ damage. The aim of the study was to investigate the endothelial markers in patients at the early stages of mild‑ to‑ moderate untreated hypertension with low‑ to‑ moderate added risk, and the effect of antihypertensive therapy by perindopril, telmisartan or rilmenidine on endothelial function.

Subjects and methods:
The measurements were carried out in 54 previously untreated hypertensive patients before and after one month of antihypertensive therapy by perindopril‑ arginine (5 mg once daily, n = 20), telmisartan (40 mg once daily, n = 16), rilmenidine (1 mg once daily, n = 18) or after placebo administration (n = 23). A population of 50 healthy normotensive subjects of similar sex, age and ethnic origin was also examined. Plasma thrombomodulin (TM) and von Willebrand factor (vWF) measurements were used as indicators of endothelial dysfunction.

Results:
In untreated hypertensive patients compared with a control group of healthy subjects a significant increase of plasma vWF (86.26 ± 26.18 IU/ dl against 69.14 ± 18.74 IU/ dl, P < 0.001) and TM (35.98 ± 12.98 ng/ ml against 29.34 ± 9.18 ng/ ml, P < 0.01) was found. BP was reduced (P < 0.001) or normalized due to each therapy. No significant changes of endothelial markers after placebo administration were found. A decrease of plasma vWF antigen level after 1 month of therapy by perindopril (from 81.93 ± 22.07 to 72.88 ± 23.26 IU/ dl, P < 0.05) or rilmenidine (from 100.6 ± 26.09 to 86.07 ± 27.66 IU/ dl, P < 0.05) was observed. No significant changes of vWF antigen levels were found after telmisartan therapy. We failed to find any changes of plasma TM due to any therapy.

Conclusion:
Our results demonstrate that antihypertensive treatment by perindopril or rilmenidine has a favourable affect on some endothelial markers.

Key words:
hypertension –  endothelium –  perindopril –  telmisartan –  rilmenidine


Sources

1. Souček M, Kára T et al. Klinická patofyziologie hypertenze. Praha: Grada Publishing 2002.

2. Remko M. Acidity, lipophilicity, solubility, absorption, and polar surface area of some ACE inhibitors. Chem Pap 2007; 61: 133– 141.

3. Remko M. Molecular structure and stability of perindopril erbumine and perindopril L‑ arginine complexes. Eur J Med Chem 2009; 44: 101– 108.

4. Zhuo JL, Mendelsohn FA, Ohishi M. Perindopril alters vascular angiotensin‑converting enzyme, AT1 receptor, and nitric oxide synthase expression in patients with coronary heart disease. Hypertension 2002; 39: 634– 638.

5. Battershill AJ, Scott LJ. Telmisartan: a review of its use in the management of hypertension. Drugs 2006; 66: 51– 83.

6. Remko M, Walsh OA, Richards WG. Molecular structure and gas‑ phase reactivity of clonidine and rilmenidine: two layered ONIOM calculations. Phys Chem Chem Phys 2001; 3: 901– 907.

7. Bousquet P, Dontenwill M, Greney H et al. Imidazoline receptors in cardiovascular and metabolic diseases. J Cardiovasc Pharmacol 2000; 35 (Suppl 4): S21– S25.

8. Souček M. Rilmenidin. Farmakoterapie 2007; 3: 329– 337.

9. Blann AD, Naqvi T, Waite M et al. Von Willebrand factor and endothelial damage in essential hypertension. J Hum Hypertens 1993; 7: 107– 111.

10. Remkova A, Kovacova E, Prikazska M et al. Thrombomodulin as a marker of endothelium damage in some clinical conditions. Eur J Intern Med 2000; 11: 79– 84.

11. Remková A, Kratochvíľová H, Ďurina J. Impact of the therapy by renin‑angiotensin system targeting antihypertensive agents perindopril versus telmisartan on prothrombotic state in essential hypertension. J Hum Hypertens 2008; 22: 338– 345.

12. Okrucká A, Pecháň J, Kratochvíľová H. Effects of the angiotensin‑converting enzyme (ACE) inhibitor perindopril on endothelial and platelet functions in essential hypertension. Platelets 1998; 9: 63– 67.

13. Remkova A, Kratochvilova H. Effect of the new centrally acting antihypertensive agent rilmenidine on endothelial and platelet function in essential hypertension. J Hum Hypertens 2002; 16: 549– 555.

14. Lip GY, Blann AD, Edmunds E et al. Baseline abnormalities of endothelial function and thrombogenesis in relation to prognosis in essential hypertension. Blood Coagul Fibrinolysis 2002; 13: 35– 41.

15. Spencer CG, Martin SC, Felmeden DC et al. Relationship of homocysteine to markers of platelet and endothelial activation in “high risk” hypertensives: a substudy of the Anglo‑ Scandinavian Cardiac Outcomes Trial. Int J Cardiol 2004; 94: 293– 300.

16. Lee KW, Blann AD, Lip GY. High pulse pressure and nondipping circadian blood pressure in patients with coronary artery disease: Relationship to thrombogenesis and endothelial damage/ dysfunction. Am J Hypertens 2005; 18: 104– 115.

17. Vischer UM. Von Willebrand factor, endothelial dysfunction and cardiovascular disease. J Thromb Haemost 2006; 4: 1186– 1193.

18. Ceconi C, Fox KM, Remme WJ et al. EUROPA and the PERTINENT Investigators. ACE inhibition with perindopril and endothelial function. Results of a substudy of the EUROPA study: PERTINENT. Cardiovasc Res 2007; 73: 237– 246.

19. Weir MR. Targeting mechanisms of hypertensive vascular disease with dual calcium channel and renin‑angiotensin system blockade. J Hum Hypertens 2007; 21: 770– 779.

20. Ghiadoni L, Magagna A, Versari D et al. Different effect of antihypertensive drugs on conduit artery endothelial function. Hypertension 2003; 41: 1281– 1286.

21. Matsumoto T, Minai K, Horie H et al. Angiotensin‑converting enzyme inhibition but not angiotensin II type 1 receptor antagonism augments coronary release of tissue plasminogen activator in hypertensive patients. J Am Coll Cardiol 2003; 41: 1373– 1379.

22. Taddei S, Virdis A, Ghiadoni L et al. Effects of antihypertensive drugs on endothelial dysfunction: clinical implications. Drugs 2002; 62: 265– 284.

23. Remková A, Kratochvíľová H. Effect of the angiotensin‑converting enzyme inhibitor perindopril on haemostasis in essential hypertension. Blood Coagul Fibrinolysis 2000; 11: 641– 644.

24. Kishi Y, Ohta S, Kasuya N et al. Perindopril augments ecto‑ ATP diphosphohydrolase activity and enhances endothelial anti‑platelet function in human umbilical vein endothelial cells. J Hypertens 2003; 21: 1347– 1353.

Labels
Diabetology Endocrinology Internal medicine

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Internal Medicine

Issue 12

2010 Issue 12

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