Rational Pharmacotherapy in Cardiology

Advanced search


Full Text:

About the Authors

S. R. Willoughby


S. Rajendran


W. P. Chan


N. Procter


S. Leslie


E. A. Liberts


T. Heresztyn


Y. Y. Chirkov


J. D. Horowitz



1. Yusuf S, Sleight P , Pogue J, Bosch J, Davies R, Dagenais G, for the Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor , ramipril, on cardiovascular events in high-risk patients. N Engl J Med 2000;342:145–53.

2. Fox KM. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet 2003;362:782–8.

3. Bakris GL, Bhandaru S, Akerstrom V, Re RN. ACE inhibitormediated attenuation of mesangial cell growth. A role for endothelin. Am J Hypertens 1994;7:583–90.

4. Soejima H, Ogawa H, Yasue H, et al. Angiotensin-converting enzyme inhibition reduces monocyte chemoattractant protein-1 and tissue factor levels in patients with myocardial infarction. J Am Coll Cardiol 1999;34:983–8.

5. Beckwith C, Munger MA. Effect of angiotensin-converting enzyme inhibitors on ventricular remodeling and survival following myocardial infarction. Ann Pharmacother 1993;27:755–66.

6. Sihm I, Schroeder AP , Aalkjaer C, et al. Normalization of structural cardiovascular changes during antihypertensive treatment with a regimen based on the ACE-inhibitor perindopril. Blood Press 1995;4: 241–8.

7. Wingler K, Wunsch S, Kreutz R, Rothermund L, Paul M, Schmidt HH. Upregulation of the vascular NAD(P)H-oxidase isoforms Nox1 and Nox4 by the renin-angiotensin system in vitro and in vivo. Free Radic Biol Med 2001;31:1456–64.

8. Mancini GB, Henry GC, Macaya C, et al. Angiotensin-converting enzyme inhibition with quinapril improves endothelial vasomotor dysfunction in patients with coronary artery disease. The TREND (Trial on Reversing ENdothelial Dysfunction) study. Circulation 1996;94:258–65.

9. The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med 1987;316:1429–35.

10. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991;325:293–302.

11. Pfeffer MA, Braunwald E, Moye LA, et al., for the SAVE Investigators. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of thesurvival and ventricular enlargement trial. N Engl J Med 1992;327: 669–77.

12. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet 1993;342:821–8.

13. Schieffer B, Bunte C, Witte J, et al. Comparative effects of AT1- antagonism and angiotensin-converting enzyme inhibition on markers of inflammation and platelet aggregation in patients with coronary artery disease. J Am Coll Cardiol 2004;44:362–8.

14. Gibbs CR, Blann AD, Watson RD, Lip GY . Abnormalities of hemorheological, endothelial, and platelet function in patients with chronic heart failure in sinus rhythm: effects of angiotensin-converting enzyme inhibitor and beta-blocker therapy. Circulation 2001;103: 1746–51.

15. Chirkov YY , Holmes AS, Martelli JD, Horowitz JD. Effect of perindopril on platelet nitric oxide resistance in patients with chronic heart failure secondary to ischemic left ventricular dysfunction. Am J Cardiol 2004;93:1438–40.

16. Chirkov YY , Horowitz JD. Impaired tissue responsiveness to organic nitrates and nitric oxide: a new therapeutic frontier? Pharmacol Ther 2007;116:287–305.

17. Chirkov YY , Holmes AS, Chirkova LP , Horowitz JD. Nitrate resistance in platelets from patients with stable angina pectoris. Circulation 1999;100:129–34.

18. Chirkov YY , Holmes AS, Willoughby SR, et al. Stable angina and acute coronary syndromes are associated with nitric oxide resistance in platelets. J Am Coll Cardiol 2001;37:1851–7.

19. Willoughby SR, Stewart S, Chirkov YY , Kennedy JA, Holmes AS, Horowitz JD. Beneficial clinical effects of perhexiline in patients with stable angina pectoris and acute coronary syndromes are associated with potentiation of platelet responsiveness to nitric oxide. Eur Heart J 2002;23:1946–54.

20. Anfossi G, Russo I, Massucco P , Mattiello L, Trovati M. Platelet resistance to the antiaggregating effect of N-acetyl-L-cysteine in obese, insulin-resistant subjects. Thromb Res 2003;110:39–46.

21. Willoughby SR, Stewart S, Holmes AS, Chirkov YY , Horowitz JD. Platelet nitric oxide responsiveness: a novel prognostic marker in acute coronary syndromes. Arterioscler Thromb Vasc Biol 2005;25:2661– 6.

22. Heresztyn T, Worthley MI, Horowitz JD. Determination of l-arginine and NG, NG- and NG, NG’ -dimethyl-L-arginine in plasma by liquid chromatography as AccQ-Fluor fluorescent derivatives. J Chromatogr B Analyt Technol Biomed Life Sci 2004;805:325–9.

23. O’Rourke MF , Gallagher DE. Pulse wave analysis. J Hypertens Suppl 1996;14:S147–57.

24. Wilkinson IB, Fuchs SA, Jansen IM, et al. Reproducibility of pulse wave velocity and augmentation index measured by pulse wave analysis. J Hypertens 1998;16:2079–84.

25. Arstall MA, Yang J, Stafford I, Betts WH, Horowitz JD. N-acetylcysteine in combination with nitroglycerin and streptokinase for the treatment of evolving acute myocardial infarction. Safety and biochemical effects. Circulation 1995;92:2855–62.

26. Chirkov YY , Chirkova LP , Horowitz JD. Nitroglycerin tolerance at the platelet level in patients with angina pectoris. Am J Cardiol 1997;80:128–31.

27. Chirkov YY , Chirkova LP , Horowitz JD. Suppressed anti-aggregating and cGMP-elevating effects of sodium nitroprusside in platelets from patients with stable angina pectoris. Naunyn Schmiedebergs Arch Pharmacol 1996;354:520–5.

28. Miller TW, Isenberg JS, Roberts DD. Thrombospondin-1 is an inhibitor of pharmacological activation of soluble guanylate cyclase. Br J Pharmacol;159:1542–7.

29. Rajendran S, Willoughby SR, Chan WP , et al. Polycystic ovary syndrome is associated with severe platelet and endothelial dysfunction in both obese and lean subjects. Atherosclerosis 2009;204:509–14.

30. Schachinger V, Zeiher AM. Quantitative assessment of coronary vasoreactivity in humans in vivo. Importance of baseline vasomotor tone in atherosclerosis. Circulation 1995;92:2087–94.

31. Adams MR, Robinson J, McCredie R, et al. Smooth muscle dysfunction occurs independently of impaired endothelium-dependent dilation in adults at risk of atherosclerosis. J Am Coll Cardiol 1998;32: 123–7.

32. Chirkov YY , Holmes AS, Willoughby SR, Stewart S, Horowitz JD. Association of aortic stenosis with platelet hyperaggregability and impaired responsiveness to nitric oxide. Am J Cardiol 2002;90:551–4.

33. Woods JD, Edwards JS, Ritter JM. Inhibition by nitroprusside of platelet calcium mobilization: evidence for reduced sensitivity to nitric oxide in essential hypertension. J Hypertens 1993;11:1369–73.

34. Liberts EA, Willoughby SR, Kennedy JA, Horowitz JD. Effects of perhexiline and nitroglycerin on vascular , neutrophil and platelet function in patients with stable angina pectoris. Eur J Pharmacol 2007;560:49–55.

35. Worthley MI, Holmes AS, Willoughby SR, et al. The deleterious effects of hyperglycemia on platelet function in diabetic patients with acute coronary syndromes mediation by superoxide production, resolution with intensive insulin administration. J Am Coll Cardiol 2007;49:304–10.

36. Schachinger V, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation 2000;101:1899–906.

37. Brugts JJ, Isaacs A, Boersma E, et al. Genetic determinants of treatment benefit of the angiotensin-converting enzyme-inhibitor perindopril in patients with stable coronary artery disease. Eur Heart J 2010;31:1854–64.

38. Rueckschloss U, Quinn MT, Holtz J, Morawietz H. Dose-dependent regulation of NAD(P)H oxidase expression by angiotensin II in human endothelial cells: protective effect of angiotensin II type 1 receptor blockade in patients with coronary artery disease. Arterioscler Thromb Vasc Biol 2002;22:1845–51.

39. Whittle BJ, Lopez-Belmonte J, Rees DD. Modulation of the vasodepressor actions of acetylcholine, bradykinin, substance P and endothelin in the rat by a specific inhibitor of nitric oxide formation. Br J Pharmacol 1989;98:646–52.


For citations:

Willoughby S.R., Rajendran S., Chan W.P., Procter N., Leslie S., Liberts E.A., Heresztyn T., Chirkov Y.Y., Horowitz J.D. RAMIPRIL SENSITAZES PLATELETS TO NITRIC OXIDE. IMPLICATION FOR THERAPY IN HIGH-RISK PATIENTS. Rational Pharmacotherapy in Cardiology. 2012;8(4):595-603. (In Russ.)

Views: 581

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)