Modifications produced by indomethacin and L-NAME in the effect of ultralow-dose aspirin on platelet activity in portal hypertension.
In our previous study, we demonstrated the effect of ultralow-dose aspirin (ULDA) on platelet activity and bleeding in rats with portal hypertension (PHT) produced by portal vein ligation (PVL). This paper reports modifications in this effect caused by blocking NO production by nitro arginine methyl ester (NAME) and cyclooxygenase (COX) activity with indomethacin. PVL rats and sham-operated controls were treated with placebo, indomethacin or NAME and 30 min thereafter with placebo or ULDA treatment. Platelet activity was studied by a model of in vivo laser-induced thrombus production in the mesenteric circulation, induced hemorrhage time (IHT) and platelet aggregation ex vivo induced by adenosine diphosphate in an aggregometer. The PVL group receiving placebo showed a decreased platelet activity with prolonged IHT, an effect that was reversed by ULDA. Indomethacin induced a decreased platelet activity in the control rats and a prolonged IHT. In PHT with ULDA, in vivo platelet activity was enhanced but the normalization of IHT observed in rats without indomethacin was blunted. The addition of NAME normalized the diminished in vivo platelet aggregation and increased the IHT observed in PVL animals. These changes decreased the effect of ULDA in both sham-operated and PVL animals. The effect of indomethacin was more clearly modified by ULDA than the effect of NAME, thus suggesting that modifications in the COX pathway might alter the effect of ULDA. The simultaneous administration of indomethacin and ULDA could inhibit its beneficial effect on bleeding in rats with PHT.
Eizayaga
Francisco X
FX
Facultad de Medicina, Universidad Maimónides, Buenos Aires, Argentina.
Aguejouf
Omar
O
Desplat
Vanessa
V
Belon
Philippe
P
Doutremepuich
Christian
C
D000818:Animals; D001241:Aspirin / Q000008:administration & dosage* / Q000494:pharmacology; D001780:Blood Coagulation Tests; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D004347:Drug Interactions; D006975:Hypertension, Portal / Q000188:drug therapy*; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015539:Platelet Activation / Q000187:drug effects*; D010979:Platelet Function Tests; D051381:Rats; D017208:Rats, Wistar; D013152:Splanchnic Circulation; D013927:Thrombosis
D016861:Cyclooxygenase Inhibitors; D009569:Nitric Oxide; D001241:Aspirin; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin