Complexes of Nitric Oxide with Nucleophiles as Agents for the Controlled Biological Release of Nitric Oxide: Antiplatelet Effect

Jean G Diodati; Arshed A Quyyumi; Nabeen Hussain; Larry K Keefer

doi:10.1055/s-0038-1649644

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1993; 70(04): 654-658
DOI: 10.1055/s-0038-1649644

Original Article

Platelets

Schattauer GmbH Stuttgart

Complexes of Nitric Oxide with Nucleophiles as Agents for the Controlled Biological Release of Nitric Oxide: Antiplatelet Effect

Jean G Diodati

¹The Cardiology Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA

,

Arshed A Quyyumi

¹The Cardiology Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA

,

Nabeen Hussain

¹The Cardiology Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA

,

Larry K Keefer

²Chemistry Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland, USA

› Author Affiliations

Abstract

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Summary

Nitric oxide (NO) inhibits platelet aggregation. Accordingly, we hypothesized that complexes of diethylamine and spermine with NO (DEA/NO and SPER/NO, respectively), two vasodilators previously shown to release NO spontaneously in aqueous solution, may also be useful antiplatelet agents. Platelet aggregation was measured in whole blood or platelet-rich plasma by impedance aggregometry after addition of collagen. In whole blood, the dose response curve for DEA/NO added 1 min before collagen was similar to that for aspirin (60% inhibition at 10^-4 M), while SPER/NO and sodium nitroprusside were less potent by an order of magnitude. In platelet-rich plasma, 10^-6 M DEA/NO caused 60% inhibition, while SPER/NO and sodium nitroprusside were as active only at 10^-5 M; aspirin’s potency was unchanged from that in whole blood. In vivo, DEA/NO and sodium nitroprusside produced significant platelet inhibition 1 min after intravenous injection in the rabbit at 50 nmol/kg. Similar in vivo platelet inhibition was observed with SPER/NO and aspirin, but only at higher dose. The effects of DEA/NO and sodium nitroprusside were transient, lasting less than 30 min after treatment, while the activity of SPER/NO and aspirin was sustained throughout the 30 min experiment. The magnitude and duration of the antiplatelet effects of DEA/NO and SPER/NO correlate with the rates at which they release nitric oxide spontaneously in aqueous solution. Thus, NO/nucleophile complexes merit further exploration both as research tools and as potential antiplatelet agents.

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References

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