Impaired NO release from bovine aortic endothelial cells exposed to activated platelets.
We have previously shown that aggregated human platelets elicited a decrease in intracellular adenosine triphosphate (ATP), enhanced adenosine egress and damage to mitochondria in bovine aortic endothelial cells (ECs). To test whether such metabolic and ultrastructural changes could be associated with functional impairment of ECs, we investigated the effects of activated platelets on nitric oxide (NO) and prostacyclin release, and on the antiaggregation property of ECs. Pretreatment of ECs with aggregated platelets transiently stimulated basal NO release while prolonged (> or = 30 min) exposure dose-dependently inhibited NO release, both basal and in response to ATP or serotonin, with NO synthase activity being attenuated in these cells. Supplementary L-arginine (L-A) restored NO release completely. Prostacyclin release was also stimulated transiently but not affected by prolonged pretreatment. The antiaggregation property of ECs was attenuated by pretreatment with activated platelets but restored with L-A supplement. Although the effects of activated platelets and 0.5 mM acetylsalicylic acid (ASA) to attenuate the antiaggregation property of ECs were additive, activated platelets had no effect on ECs treated with 0.2 mM N omega-nitro-L-arginine (L-NA), suggesting a common mechanism. We conclude that prolonged exposure to aggregated platelets may affect the antiaggregation property of ECs by directly inhibiting NO synthesis, which may be normalized by L-A supplementation.
Watanabe
R
R
Third Department of Medicine, Tokyo Medical and Dental University, Japan.
Kishi
Y
Y
Sakita
S
S
Numano
F
F
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D001120:Arginine / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D015539:Platelet Activation; D010974:Platelet Aggregation; D012701:Serotonin / Q000494:pharmacology
D019335:Nitroarginine; D009569:Nitric Oxide; D012701:Serotonin; D000255:Adenosine Triphosphate; D001120:Arginine; D011464:Epoprostenol; D019001:Nitric Oxide Synthase