Platelet inhibitory effect of nitroglycerin in platelet-rich plasma: relevance of glutathione-s-transferases in plasma.
BACKGROUND
Nitroglycerin (NTG) is believed to exert its platelet inhibitory effect via its biotransformation to nitric oxide (NO). We examined the relevance of glutathione-s-transferases (GST) in plasma in the conversion of NTG to NO and the platelet inhibitory effect of NTG.


RESULTS
Nitroglycerin (1-100 micrograms/mL) was incubated with human platelet-rich plasma (PRP) for 10-60 minutes. Nitroglycerin caused a concentration-dependent inhibition of platelet aggregation in PRP with IC50 approximately 50 micrograms/mL. NTG also enhanced nitrite levels in PRP and stimulated cyclic GMP accumulation in platelets. In contrast, when NTG was incubated with washed platelets (WP) in concentrations as high as 100 micrograms/mL, there was no inhibition of platelet aggregation, formation of nitrite, or accumulation of cGMP. However, treatment of WP suspension with authentic NO exhibited diminished platelet aggregation, suggesting that NTG delivers NO in plasma that subsequently inhibits platelet aggregation. In keeping with this concept, the aggregation inhibitory effect of NTG in PRP was blocked by oxyhemoglobin. The platelet aggregation inhibition by NTG was potentiated by propylthiouracil (600 micrograms/mL), a GST inducer, and antagonized by ketoprofen (100 micrograms/mL), a GST inhibitor. Direct measurement indeed showed significant GST activity in plasma (24 +/- 3 mU/mL).


CONCLUSIONS
We suggest that NTG inhibits platelet aggregation in PRP by its biotransformation to NO in plasma. The presence of GST, and perhaps other cofactors, in plasma is relevant in the platelet inhibitory effects of NTG in PRP.
Chen
L Y
LY
Department of Medicine, University of Florida College of Medicine, Gainesville 32610-0277, USA.
Mehta
P
P
Mehta
J L
JL
D000328:Adult; D001711:Biotransformation; D004353:Drug Evaluation, Preclinical; D005982:Glutathione Transferase / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D009569:Nitric Oxide / Q000494:pharmacology; D005996:Nitroglycerin / Q000378:metabolism / Q000494:pharmacology*; D010949:Plasma / Q000201:enzymology*; D010974:Platelet Aggregation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology*
D014665:Vasodilator Agents; D009569:Nitric Oxide; D005982:Glutathione Transferase; D005996:Nitroglycerin