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Antiplatelet effects of a novel antianginal agent, nicorandil.
- Source :
-
Journal of cardiovascular pharmacology [J Cardiovasc Pharmacol] 1994 Jan; Vol. 23 (1), pp. 24-30. - Publication Year :
- 1994
-
Abstract
- Nicorandil (nicotinamidoethyl nitrate) is a novel vasodilator. Its vasodilator properties are related both to the nicotinamide and nitrate moieties. Classic nitrates such as nitroglycerin (NTG) and isosorbide dinitrate demonstrate in vitro inhibition of ADP-induced platelet aggregation. Such effects have been shown to occur in a dose-related manner, are potentiated by reduced thiols and by increasing preincubation time, and are associated with increases in intracellular cyclic GMP. We explored the effect of nicorandil on ADP-induced human platelet aggregation and the role of reduced thiol N-acetylcysteine (NAC) in modulating this response. Nicorandil significantly inhibited aggregation to ADP dose dependently (IC50 3.0 mM). These effects were associated with inhibition of fibrinogen binding to the platelet surface (IC50 2 mM). Addition of nicorandil after maximal ADP-induced aggregation was achieved resulted in disaggregation. Addition of a source of reduced thiol (NAC) potentiated the antiaggregatory effects of nicorandil threefold (p < 0.05). Platelet inhibition by nicorandil was also augmented by increase in duration of preincubation, with maximal effects observed at 180 min. Preincubation of platelets with 10 mM nicorandil resulted in attenuated inhibition of platelet aggregation on gel filtration and subsequent exposure to additional nicorandil, indicative of tolerance induction. Methylene blue (MB), an inhibitor of guanylate cyclase, significantly reversed nicorandil-induced inhibition of platelet aggregation. Moreover, in accordance with this mechanism, nicorandil increased intracellular platelet cyclic GMP levels. Although the antiplatelet effect of nicotinamide was partially reversed by the K+ channel inhibitor iberotoxin, preincubation with iberotoxin had no impact on inhibition of platelet aggregation by nicorandil.(ABSTRACT TRUNCATED AT 250 WORDS)
- Subjects :
- Acetylcysteine pharmacology
Adenosine Diphosphate pharmacology
Analysis of Variance
Binding Sites
Blood Platelets metabolism
Cyclic GMP blood
Dose-Response Relationship, Drug
Drug Tolerance
Fibrinogen metabolism
Guanylate Cyclase blood
Humans
Niacinamide pharmacology
Nicorandil
Potassium Channels drug effects
Potassium Channels physiology
Radioimmunoassay
Blood Platelets drug effects
Niacinamide analogs & derivatives
Platelet Aggregation drug effects
Platelet Aggregation Inhibitors pharmacology
Vasodilator Agents pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0160-2446
- Volume :
- 23
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of cardiovascular pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 7511731
- Full Text :
- https://doi.org/10.1097/00005344-199401000-00024