title: Platelet function is inhibited by nitric oxide liberation during nitroglycerin-induced hypotension anaesthesia.
abstract: The inhibitory effects of nitroglycerin (NTG) on platelet function and the mechanisms of inhibition have been studied in vitro, but not in vivo. Therefore, we have investigated the effects of NTG on platelet function in eight patients undergoing orthopaedic surgery. Simultaneous measurements of platelet aggregation and change in intracellular calcium concentrations were performed in Fura-2 loaded platelets using thrombin as a stimulator. Intraplatelet concentrations of cyclic 3',5'-guanine monophosphate (cGMP) were measured by radioimmunoassay, and the concentration of nitrite ion was also measured. Continuous i.v. infusion of NTG 4-8 micrograms kg-1 min-1 significantly inhibited platelet aggregation and the increase in intracellular Ca2+ concentration (first phase, mean 439.9 (SEM 68.7) vs 210.6 (38.7) nmol litre-1; second phase, 154.4 (19.8) vs 106.7 (18.0) nmol litre-1). The concentration of cGMP (from 0.633 (0.098) to 1.764 (0.578) pmol/10(9) platelets) and the concentration of nitrite ion (from 532.6 (17.6) to 724.4 (34.8) nmol litre-1) also increased significantly after infusion of NTG. The NTG concentration in plasma was of the order of 10(-8) mol litre-1. We have demonstrated that in vivo, NTG increased intraplatelet cGMP concentrations and inhibited platelet function; one mechanisms of this effect is likely to be related to nitric oxide liberation from NTG bioconversion.
authors.affiliation: Department of Anaesthesiology, Kyoto Prefectural University of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Aoki
authors.forename: M
authors.initials: M
authors.lastname: Inoue
authors.forename: T
authors.initials: T
authors.lastname: Mizobe
authors.forename: M
authors.initials: M
authors.lastname: Harada
authors.forename: H
authors.initials: H
authors.lastname: Imai
authors.forename: A
authors.initials: A
authors.lastname: Kobayashi
mesh_terms: D000328:Adult; D000368:Aged; D000768:Anesthesia, General; D001760:Bleeding Time; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000097:blood; D006152:Cyclic GMP / Q000097:blood; D005260:Female; D006801:Humans; D007023:Hypotension, Controlled; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology; D005996:Nitroglycerin / Q000097:blood / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000097:blood / Q000494:pharmacology*
chemical_list: D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; D009569:Nitric Oxide; D005996:Nitroglycerin; D006152:Cyclic GMP; D002118:Calcium