Simultaneous inhibition of TxA2 and PGI2 synthesis increases NO release in mesenteric resistance arteries from cirrhotic rats
Résumé
Our study examines, in mesenteric resistance arteries, possible vasodilation alterations, and the role of NO and COX-derivates in cirrhosis. Vasodilator response to acetylcholine was analysed in segments from control and cirrhotic rats. The effects of the unspecific COX inhibitor indomethacin, of the specific COX-1 inhibitor SC-560 and of the specific COX-2 inhibitor NS-398 were analysed in segments from both groups of rats. NO release was measured and eNOS, phosphorylated eNOS (P-eNOS), iNOS, COX-1 and COX-2 expressions were also analysed. The effects of TP receptor antagonist SQ 29548, TxA2 synthesis inhibitor furegrelate, of PGI2 synthesis inhibitor TCP or of TCP-plus-furegrelate were only determined in segments from cirrhotic rats. Vasodilator response to acetylcholine was higher in segments from cirrhotic rats. Indomethacin, SC-560 and NS-398 did not modify vasodilator response in control rats However, indomethacin, NS-398 and TCP-plus-furegrelate increased, SC-560 did not modify, and SQ 29548, furegrelate or TCP decreased the vasodilator response to acetylcholine in cirrhotic rats. NO release was higher in cirrhotic rats. Furegrelate decreased, while TCP-plus-furegrelate increased the NO release in segments from cirrhotic rats. eNOS and COX-1 expression were not modified, while P-eNOS, iNOS and COX-2 expression were higher in cirrhotic rats. The increased iNOS expression and eNOS activity mediate increases in endothelial NO release. The COX-2 derivates TxA2 and PGI2 act simultaneously, producing a compensatory effect that reduces NO release and may limit hyperdynamic circulation.
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