Please use this identifier to cite or link to this item:
Scopus Web of Science® Altmetric
Type: Journal article
Title: Ramipril sensitizes platelets to nitric oxide: Implications for therapy in high-risk patients
Author: Willoughby, S.
Rajendran, S.
Chan, W.
Procter, N.
Leslie, S.
Liberts, E.
Heresztyn, T.
Chirkov, Y.
Horowitz, J.
Citation: Journal of the American College of Cardiology, 2012; 60(10):887-894
Publisher: Elsevier Science Inc
Issue Date: 2012
ISSN: 0735-1097
Statement of
Scott R. Willoughby, Sharmalar Rajendran, Wai P. Chan, Nathan Procter, Sue Leslie, Elizabeth A. Liberts, Tamila Heresztyn, Yuliy Y. Chirkov, John D. Horowitz
Abstract: Using 2 sequential studies in HOPE (Heart Outcomes Prevention Evaluation) study-type patients, the aims of this study were: 1) to test the hypothesis that ramipril improves platelet nitric oxide (NO) responsiveness: and 2) to explore biochemical and physiological effects of ramipril in a cohort selected on the basis of platelet NO resistance.Ramipril prevents cardiovascular events, but the bases for these effects remain uncertain. NO resistance at both the platelet and vascular levels is present in a substantial proportion of patients with diabetes or ischemic heart disease and is an independent risk factor for cardiovascular events.Study 1 was a double-blind, randomized comparison of ramipril (10 mg) with placebo in a cohort of patients (n = 119) with ischemic heart disease or diabetes plus additional coronary risk factor(s), in which effects on platelet responsiveness to NO were compared. Study 2 was a subsequent short-term evaluation of the effects of ramipril in a cohort of subjects (n = 19) with impaired platelet NO responsiveness in whom additional mechanistic data were sought.In study 1, ramipril therapy increased platelet responsiveness to NO relative to the extent of aggregation (p < 0.001), but this effect occurred primarily in patients with severely impaired baseline NO responsiveness (n = 41). In study 2, ramipril also improved platelet NO responsiveness (p < 0.01), and this improvement was correlated directly with increased NO-stimulated platelet generation of cyclic guanosine monophosphate (p < 0.02) but not with changes in plasma thrombospondin-1 levels.Ramipril ameliorates platelet NO resistance in HOPE study-type patients, with associated increases in soluble guanylate cyclase responsiveness to NO. This effect is likely to contribute to treatment benefit and define patients in whom ramipril therapy is particularly effective.
Keywords: Blood Platelets; Humans; Nitroprusside; Nitric Oxide; Malondialdehyde; Ramipril; Guanylate Cyclase; Arginine; Thrombospondin 1; Cyclic GMP; Adenosine Diphosphate; Angiotensin-Converting Enzyme Inhibitors; Drug Administration Schedule; Cohort Studies; Double-Blind Method; Oxidative Stress; Platelet Aggregation; Aged; Aged, 80 and over; Middle Aged; Female; Male; Biomarkers
Rights: Copyright © 2012 American College of Cardiology Foundation
RMID: 0020121785
DOI: 10.1016/j.jacc.2012.01.066
Grant ID:
Appears in Collections:Medicine publications

Files in This Item:
There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.