Effect of trilinolein on cyclic nucleotide formation in human platelets: relationship with its antiplatelet effect and nitric oxide synthesis

Abstract

Trilinolein, a triacylglycerol with linoleic acid as the only fatty acid residue in all three esterified positions of glycerol, was recently reported to have an inhibitory effect on adrenaline‐induced platelet aggregation. In the present study, we found that trilinolein at concentrations ranging from 0.01 to 1 μM. increased cyclic GMP formation and decreased cyclic AMP formation in washed human platelets. Both NG‐nitro‐L‐arginine methyl ester (L‐NAME) and methylene blue attenuated the trilinolein‐induced increase in cyclic GMP. Adrenaline decreased not only the production of cyclic AMP but also that of cyclic GMP. Trilinolein antagonized the inhibitory effect of adrenaline on cyclic GMP formation, but potentiated the inhibitory effect of adrenaline on cyclic AMP accumulation. Both trilinolein and adrenaline enhanced intracellular calcium but the increment of intracellular calcium induced by them was much less than that produced by thrombin. We propose that the anti‐platelet effect of trilinolein is mediated through an increase in cyclic GMP, and that the change in cyclic GMP results from stimulation of nitric oxide synthesis in platelets. We also propose that reduction of both cyclic AMP and cyclic GMP are involved in adrenaline‐induced platelet aggregation.

Effect of Trilinolein on Strophanthidin-Induced Ventricular Tachycardia in Guinea Pigs

“…Moreover, the doses of strophanthidin required to induce ventricular tachycardia were not different in the guinea pigs pretreated with or without trilinolein. There are several possibilities to account for the results: (1) the effect of trilinolein on Ca 2+ inward current may be not strong enough to prevent Ca 2+ overload; in this study, unlike the Ca 2+ antagonists, treatment with trilinolein did not increase the risk of atrioventricular block in strophanthidin administration [17]; this result suggests that the Ca 2+ antagonist activity of trilinolein is relatively weak; (2) in the report of Shen and Hong [23], 0.01 or 0.1 Ìmol/l trilinolein would result in a significant increase in cytosolic Ca 2+ in human platelets; it is possible that the effects of different doses of trilinolein on different tissues or different experimental models vary widely; (3) this laboratory and other investigators found that termination of digitalis-induced ventricular tachycardia was also related to the inhibition of digitalis-induced enhanced sympathetic activity [18,24]. Although unpublished data [Chi and Su, pers.…”

Protective effects of (6R)-5,6,7,8-tetrahydro-L-biopterin on local ischemia/reperfusion-induced suppression of reactive hyperemia in rat gingiva

“…( 4 – 6 ) NO is produced from l -arginine as a substrate by nitric oxide synthase (NOS). The physiological actions of NO are not limited to vascular smooth muscle relaxation, ( 7 , 8 ) they have been shown to extend to antiplatelet aggregation, ( 9 ) neurotransmission, ( 10 ) immune reactions, ( 11 ) and apoptosis. ( 12 )…”