title: Simultaneous inhibition of TXA(2) and PGI(2) synthesis increases NO release in mesenteric resistance arteries from cirrhotic rats.
abstract: 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 A(2)) receptor] antagonist SQ 29548, the TXA(2) synthesis inhibitor furegrelate, the PGI(2) (prostaglandin I(2)) 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 TXA(2) and PGI(2) may act simultaneously, producing a compensatory effect that reduces NO release and may limit the hyperdynamic circulation.
authors.affiliation: Departamento de Fisiologia e Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Recife 50670-420, Brazil.
authors.forename: Fabiano E
authors.initials: FE
authors.lastname: Xavier
authors.forename: Javier
authors.initials: J
authors.lastname: Blanco-Rivero
authors.forename: Esther
authors.initials: E
authors.lastname: Sastre
authors.forename: Lina
authors.initials: L
authors.lastname: Badimón
authors.forename: Gloria
authors.initials: G
authors.lastname: Balfagón
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D002097:C-Reactive Protein / Q000378:metabolism; D050356:Lipid Metabolism / Q000502:physiology; D008099:Liver / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009929:Organ Size / Q000502:physiology; D011453:Prostaglandins / Q000378:metabolism; D011454:Prostaglandins A / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000473:pathology; D013481:Superoxides / Q000378:metabolism; D013928:Thromboxane A2 / Q000096:biosynthesis / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology
chemical_list: D011453:Prostaglandins; D011454:Prostaglandins A; D013481:Superoxides; D009569:Nitric Oxide; D013928:Thromboxane A2; D002097:C-Reactive Protein; C100008:prostaglandin A2