SUSTAINED ANTIPLATELET PROPERTIES OF NITROGLYCERIN DURING HEMODYNAMICTOLERANCE IN RATS

Organic nitrates possess important antiplatelet actions that are usefu l in the treatment of unstable angina and myocardial infarction, but t he susceptibility of platelets to nitrate tolerance has not been exten sively studied. In normal conscious rats, we showed that continuous in fusion of nitroglycerin (NTG) at 10 mu g/min had no significant effect on mean arterial pressure (MAP) as compared with control, but hemodyn amic tolerance could be demonstrated by MAP response to a bolus intrav enous (i.v.) NTG challenge, By this criterion, continuous 8-h NTG infu sion produced hemodynamic tolerance (a decrease in MAP response of 45. 7 +/- 19.9%, p < 0.05), whereas D5W control and S-nitroso-N-acetylpeni cillamine (SNAP) infusions did not. During NTG infusion, platelet-rich plasma (PRP) cyclic GMP was increased by 41.4 +/- 13.6% as compared w ith 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 com pared to 3.8 +/- 0.3 min in controls (p < 0.05). After 8-h of NTG infu sion, 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 concentratio n by 30% in 8 h, whereas D5W had no effect. In vitro experiments showe d that platelets in themselves do not produce significant amounts of c yclic GMP. These data indicate that the biochemical and antiaggregatio n effects of NTG on platelets are not diminished during hemodynamic to lerance and that these effects may be dependent on extraplatelet produ ction of nitric oxide (NO).