Our present study examines, in mesenteric resistance arteries, possible vasodilation alterations, and the role of NO and COX (cyclo-oxygenase) derivatives, in cirrhosis. The vasodilator response to acetylcholine was analysed in segments from control and cirrhotic rats. The effects of the non-specific COX inhibitor indomethacin, the specific COX-1 inhibitor SC-560 and the specific COX-2 inhibitor NS-398 were analysed in segments from both groups of rats. NO release was measured, and eNOS [endothelial NOS (NO synthase)], phospho-eNOS, iNOS (inducible NOS), COX-1 and COX-2 protein expression was also analysed. The effects of the TP receptor [TXA2 (thromboxane A2) receptor] antagonist SQ 29548, the TXA2 synthesis inhibitor furegrelate, the PGI2 (prostaglandin I2) synthesis inhibitor TCP (tranylcypromine) or TCP+furegrelate were only determined in segments from cirrhotic rats. The vasodilator response to acetylcholine was higher in segments from cirrhotic rats. Indomethacin, SC-560 and NS-398 did not modify the vasodilator response in control rats; however, indomethacin, NS-398 and TCP+furegrelate increased, whereas 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, whereas TCP+furegrelate increased, the NO release in segments from cirrhotic rats. eNOS and COX-1 protein expression was not modified, whereas phosho-eNOS, iNOS and COX-2 protein expression was higher in cirrhotic rats. Therefore the increase in iNOS expression and eNOS activity may mediate increases in endothelial NO release. The COX-2 derivatives TXA2 and PGI2 may act simultaneously, producing a compensatory effect that reduces NO release and may limit the hyperdynamic circulation.
Simultaneous inhibition of TXA2 and PGI2 synthesis increases NO release in mesenteric resistance arteries from cirrhotic rats
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Fabiano E. Xavier, Javier Blanco-Rivero, Esther Sastre, Lina Badimón, Gloria Balfagón; Simultaneous inhibition of TXA2 and PGI2 synthesis increases NO release in mesenteric resistance arteries from cirrhotic rats. Clin Sci (Lond) 1 October 2010; 119 (7): 283–292. doi: https://doi.org/10.1042/CS20090536
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