[Effects of the novel synthetic fatty acid dinitroglycerol esters on aggregation of the human platelets in vitro].
A series of six new synthetic dinitroglycerol esters of fatty acids on the human platelet aggregation was studied in vitro. Inclusion of the dinitroglycerol moiety into the molecule of arachidonic acid deprived this acid from pro-aggregant activity. All six compounds produced moderate (dose-dependent) inhibition of the platelet aggregation process induced by arachidonic acid (1 x 10(-3) M). Platelet aggregation was most significantly affected by dinitroglycerol esters of arachidonic and docosahexaenoic acids. This is probably explained by the influence of these esters on the oxidative metabolism of arachidonic acid to eicosanoids playing the role of proaggregants. In the presence of vessel wall (rat aorta fragments), dinitroglycerol esters of arachidonic and docosahexaenoic acids incubated with platelets (5 min, 37 degrees C) significantly reduced their aggregation induced by arachidonic acid (1 x 10(-3) M) or docosahexaenoic acid (1 x 10(-5) M) under the conditions of endothelial cyclooxygenase suppressed by acetylsalicylic acid (10 mg/ml). The pronounced antiaggregant effect of the synthetic dinitroglycerol esters studied is probably related to their ability to act as NO donors suppressing the activity of thrombocytes (provided that the NO production activity is present in the system).
Vasil'eva
T M
TM
Laboratory of Hemostasis Pathology and Pharmacology, Scientific Hematology Center, Russian Academy of Medical Sciences, Novo-Zykovskii proezd 4a, Moscow, 125167 Russia.
Petrukhina
G N
GN
Makarov
V A
VA
Serkov
I V
IV
Gretskaia
N M
NM
Bezuglov
V V
VV
D000818:Animals; D001011:Aorta; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology; D004952:Esters; D005227:Fatty Acids / Q000737:chemistry / Q000494:pharmacology*; D005990:Glycerol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009574:Nitro Compounds / Q000737:chemistry / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D016861:Cyclooxygenase Inhibitors; D004952:Esters; D005227:Fatty Acids; D009574:Nitro Compounds; D010975:Platelet Aggregation Inhibitors; D005990:Glycerol