Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/8549
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Type: Journal article
Title: Nitroglycerin tolerance at the platelet level in patients with angina pectoris.
Author: Chirkov, Y.
Chirkova, L.
Horowitz, J.
Citation: American Journal of Cardiology, 1997; 80(2):128-131
Publisher: EXCERPTA MEDICA INC
Issue Date: 1997
ISSN: 0002-9149
1879-1913
Abstract: Suppression of platelet aggregation may be an important component of the therapeutic effect of nitroglycerin (NTG). Because of the phenomenon of hemodynamic tolerance to NTG, we tested the hypothesis that the anti-platelet effects of NTG in humans are also subject to tolerance induction. In patients with stable angina who had not received nitrates for at least 24 hours before study, sublingual administration of NTG (300 microg; n = 17) attenuated the reversal of adenosine diphosphate-induced platelet aggregation by NTG applied in vitro. Three minutes after in vivo NTG administration, concentration of NTG producing 50% reversal of aggregation (C50) increased from 7.9 +/- 1.9 x 10(-5) to 5.5 +/- 0.3 x 10(-4) M (p <0.01); this change persisted for at least 60 minutes. There was no concomitant change in C50 values for sodium nitroprusside applied in vitro. Basal activity of platelet guanylate cyclase and its response to sodium nitroprusside were not affected after administration of NTG. Brief intravenous infusion of NTG (10 microg/min for 10 minutes) produced no significant changes in platelet responses to NTG in vitro. However, prolonged infusion of NTG (5 microg/min for 24 hours, patients with unstable angina pectoris, n = 11) caused suppression of in vitro platelet response to NTG. Platelets from patients receiving prophylactic nitrates (n = 19) were less responsive to the antiaggregatory effects of NTG in vitro than those from patients who had not received nitrates in the previous 24 hours (n = 21). Thus, clinical exposure to NTG, even in very low doses, induces tolerance to antiaggregatory effects of NTG. This phenomenon is not associated either with cross tolerance to sodium nitroprusside or with down-regulation of platelet guanylate cyclase.
Keywords: Blood Platelets
Humans
Angina Pectoris
Angina, Unstable
Nitroprusside
Nitrates
Nitroglycerin
Guanylate Cyclase
Administration, Sublingual
Infusions, Intravenous
Platelet Aggregation
Drug Tolerance
DOI: 10.1016/S0002-9149(97)00305-6
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