Simultaneous inhibition of TxA2 and PGI2 synthesis increases NO release in mesenteric resistance arteries from cirrhotic rats.
2010, Clin Sci (Lond). 2010 May 11. [Epub ahead of print]
Xavier FE, Blanco-Rivero J, Sastre E, Badimón L, Balfagón G.
Autors del centre relacionats: Badimon Lina.
Xavier FE, Blanco-Rivero J, Sastre E, Badimón L, Balfagón G.
Autors del centre relacionats: Badimon Lina.
Abstract
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.
PMID: 20459396 [PubMed - as supplied by publisher]
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.
PMID: 20459396 [PubMed - as supplied by publisher]
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