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(Circulation. 2000;102:e87.)
© 2000 American Heart Association, Inc.

Correspondence

Nitrate Resistance in Platelets From Patients With Stable Angina Pectoris

I. L. Megson, PhD; D. J. Webb, MD

Clinical Pharmacology Unit, University of Edinburgh, Western General Hospital, Edinburgh, UK

To the Editor:

The article by Chirkov and colleagues¹ clearly indicates that platelets in plasma samples from patients with stable angina are resistant to the inhibitory effects of pharmacological concentrations of the nitric oxide (NO) donor drugs nitroglycerine (NTG) and sodium nitroprusside (SNP). Resistance was reversed by superoxide dismutase, suggesting that the effect might be due to superoxide-mediated inactivation of NO derived from NTG and SNP in the platelets of patients.

As the authors point out, this interesting observation does not necessarily reflect platelet resistance to NTG in vivo. However, even in the absence of nitrate resistance, organic nitrates are notoriously poor inhibitors of platelet aggregation² because, unlike vascular tissue, platelets lack the necessary metabolic pathway for NO generation from nitrates.³ This issue is highlighted by the need to use high concentrations (100 µmol/L) of NTG to inhibit platelet aggregation in this study; the maximum estimated plasma concentration with transdermal and sublingual NTG is several orders of magnitude lower (2 and 20 nmol/L, respectively). Clearly, NTG is unlikely to have an impact on platelet aggregation in angina pectoris, irrespective of nitrate resistance. It is noteworthy that SNP is a significantly more potent inhibitor of platelet aggregation; perhaps we should be looking to SNP and platelet-selective NO donors such as S-nitrosothiols⁴ as vasodilators with antithrombotic activity, rather than organic nitrates.

References

1. Chirkov YY, Holmes AS, Chirkova LP, et al. Nitrate resistance in platelets from patients with stable angina pectoris. Circulation. 1999;100:129–134.[Abstract/Free Full Text]

2. Drummer C, Valta-Seufzer U, Karrenbrock B, et al. Comparison of anti-platelet properties of molsidomine, isosorbide-5-mononitrate and placebo in healthy volunteers. Eur Heart J. 1991;12:541–549.[Abstract/Free Full Text]

3. Weber A-A, Neuhaus T, Seul C, et al. Biotransformation of glyceryl trinitrate by blood platelets as compared to vascular smooth muscle cells. Eur J Pharmacol. 1996;309:209–213.[Medline] [Order article via Infotrieve]

4. De Belder AJ, MacAllister R, Radomski MW, et al. Effects of S-nitroso-glutathione in the human forearm circulation: evidence for selective inhibition of platelet activation. Cardiovasc Res. 1994;28:691–694.[Medline] [Order article via Infotrieve]

Response

Yuliy Y. Chirkov, PhD; Andrew S. Holmes, BSc, Hons; Larissa P. Chirkova, PhD; John D. Horowitz, PhD

Department of Cardiology, The Queen Elizabeth Hospital, University of Adelaide, Adelaide, SA, Australia

We thank Drs Megson and Webb for their interest in our article. With regard to the phenomenon of "nitrate resistance," it is certainly correct that reduced responsiveness to sodium . . . [Full Text of this Article]