TY - JOUR
T1 - Sustained antiplatelet properties of nitroglycerin during hemodynamic tolerance in rats
AU - Booth, Brian P.
AU - Jacob, Saji
AU - Bauer, John A.
AU - Fung, Ho Leung
PY - 1996
Y1 - 1996
N2 - Organic nitrates possess important antiplatelet actions that are useful in the treatment of unstable angina and myocardial infarction, but the susceptibility of platelets to nitrate tolerance has not been extensively studied. In normal conscious rats, we showed that continuous infusion of nitroglycerin (NTG) at 10 μg/min had no significant effect on mean arterial pressure (MAP) as compared with control, but hemodynamic tolerance could be demonstrated by MAP response to a bolus intravenous (i.v.) NTG challenge. By this criterion, continuous 8-h NTG infusion produced hemodynamic tolerance (a decrease in MAP response of 45.7 ± 19.9%, p < 0.05), whereas D5W control and S-nitroso-N-acetylpenicillamine (SNAP) infusions did not. During NTG infusion, platelet-rich plasma (PRP) cyclic GMP was increased by 41.4 ± 13.6% as compared with control and remained increased throughout the infusion (p < 0.05). Bleeding time during a 2-h infusion of NTG was 8.9 ± 1.2 min as compared to 3.8 ± 0.4 min in controls (p < 0.05). After 8-h of NTG infusion, the bleeding time was 10.2 ± 1.4 min versus 4.4 ± 0.4 min in controls (p < 0.05). NTG also decreased the PRP platelet concentration by 30% in 8 h, whereas D5W had no effect. In vitro experiments showed that platelets in themselves do not produce significant amounts of cyclic GMP. These data indicate that the biochemical and antiaggregation effects of NTG on platelets are not diminished during hemodynamic tolerance and that these effects may be dependent on extraplatelet production of nitric oxide (NO).
AB - Organic nitrates possess important antiplatelet actions that are useful in the treatment of unstable angina and myocardial infarction, but the susceptibility of platelets to nitrate tolerance has not been extensively studied. In normal conscious rats, we showed that continuous infusion of nitroglycerin (NTG) at 10 μg/min had no significant effect on mean arterial pressure (MAP) as compared with control, but hemodynamic tolerance could be demonstrated by MAP response to a bolus intravenous (i.v.) NTG challenge. By this criterion, continuous 8-h NTG infusion produced hemodynamic tolerance (a decrease in MAP response of 45.7 ± 19.9%, p < 0.05), whereas D5W control and S-nitroso-N-acetylpenicillamine (SNAP) infusions did not. During NTG infusion, platelet-rich plasma (PRP) cyclic GMP was increased by 41.4 ± 13.6% as compared with control and remained increased throughout the infusion (p < 0.05). Bleeding time during a 2-h infusion of NTG was 8.9 ± 1.2 min as compared to 3.8 ± 0.4 min in controls (p < 0.05). After 8-h of NTG infusion, the bleeding time was 10.2 ± 1.4 min versus 4.4 ± 0.4 min in controls (p < 0.05). NTG also decreased the PRP platelet concentration by 30% in 8 h, whereas D5W had no effect. In vitro experiments showed that platelets in themselves do not produce significant amounts of cyclic GMP. These data indicate that the biochemical and antiaggregation effects of NTG on platelets are not diminished during hemodynamic tolerance and that these effects may be dependent on extraplatelet production of nitric oxide (NO).
KW - Bleeding time
KW - Cyclic GMP
KW - Nitric oxide
KW - Nitroglycerin
KW - Platelets
KW - Tolerance
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U2 - 10.1097/00005344-199609000-00013
DO - 10.1097/00005344-199609000-00013
M3 - Article
C2 - 8877591
AN - SCOPUS:0029815891
SN - 0160-2446
VL - 28
SP - 432
EP - 438
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
IS - 3
ER -