Modifications produced by selective inhibitors of cyclooxygenase and ultra low dose aspirin on platelet activity in portal hypertension.
OBJECTIVE
To study the mechanism involved in the potentially beneficial effect of ultra low dose aspirin (ULDA) in prehepatic portal hypertension, rats were pretreated with selective COX 1 or 2 inhibitors (SC-560 or NS-398 respectively), and subsequently injected with ULDA or placebo.


METHODS
Portal hypertension was induced by portal vein ligation. Platelet activity was investigated with an in-vivo model of laser induced thrombus production in mesenteric circulation and induced hemorrhagic time (IHT). Platelet aggregation induced by ADP and dosing of prostanoid products 6-keto-PGF1alpha, TXB2, PGE2 and LTB4 were also performed.


RESULTS
The portal hypertensive group receiving a placebo showed a decreased in vivo platelet activity with prolonged IHT, an effect that was normalized by ULDA. SC-560 induced a mild antithrombotic effect in the normal rats, and an unmodified effect of ULDA. NS-398 had a mild prothrombotic action in portal hypertensive rats, similar to ULDA, but inhibited a further effect when ULDA was added. An increased 6-keto-PGF1alpha was observed in portal hypertensive group that was normalised after ULDA administration. TXA2 level after ULDA, remained unchanged.


CONCLUSIONS
These results suggest that the effect of ULDA on platelet activity in portal hypertensive rats, could act through a COX 2 pathway more than the COX 1, predominant for aspirin at higher doses.
Eizayaga
Francisco X
FX
Universidad Maimónides, Buenos Aires, Argentina.
Aguejouf
Omar
O
Desplat
Vanessa
V
Belon
Philippe
P
Doutremepuich
Christian
C
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006975:Hypertension, Portal / Q000097:blood*; D007834:Lasers / Q000009:adverse effects; D007975:Leukotriene B4 / Q000097:blood; D008297:Male; D009578:Nitrobenzenes / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology*; D013927:Thrombosis / Q000097:blood / Q000209:etiology; D013929:Thromboxane B2 / Q000097:blood
D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D011720:Pyrazoles; C115461:SC 560; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D007975:Leukotriene B4; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D015232:Dinoprostone; D001241:Aspirin