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Background/aims

Cirrhotic livers exhibit endothelial dysfunction that contributes to the increased hepatic vascular resistance. The present study evaluates the role of cyclooxygenase (COX)-derived prostanoids, implicated in the pathogenesis of endothelial dysfunction in other settings, in the pathogenesis of endothelial dysfunction in cirrhotic livers.

Methods

Endothelial dysfunction was evaluated by performing concentration-effect curves to acetylcholine after precontracting the liver with methoxamine in groups of control and CCl(4)-cirrhotic rat livers preincubated either with vehicle, indomethacin, the COX-1 selective inhibitor, SC-560, the COX-2 selective inhibitor, SC-236, the thromboxane A(2) receptor antagonist, SQ 29,548 or the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine. Thromboxane A(2) (TXA(2)) production was determined in samples of the perfusate.

Results

Cirrhotic livers exhibited endothelial dysfunction, as shown by the significantly lower relaxation to acetylcholine than control livers, that was totally corrected by indomethacin. COX-1 inhibition and TXA(2) blockade, but not COX-2 inhibition, also corrected endothelial dysfunction. Acetylcholine significantly increased TXA(2) production in cirrhotic but not in control livers. Indomethacin and COX-1 inhibition, but not COX-2 or NO inhibition, prevented the increased production of TXA(2).

Conclusions

An increased production of TXA(2) is involved in the pathogenesis of endothelial dysfunction in cirrhotic rat livers. This is mainly mediated by COX-1, but not by COX-2."xsd:string
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http://purl.uniprot.org/citations/12971960http://purl.uniprot.org/core/author"Abraldes J.G."xsd:string
http://purl.uniprot.org/citations/12971960http://purl.uniprot.org/core/author"Graupera M."xsd:string
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http://purl.uniprot.org/citations/12971960http://purl.uniprot.org/core/name"J Hepatol"xsd:string
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http://purl.uniprot.org/citations/12971960http://purl.uniprot.org/core/title"Cyclooxygenase-1 inhibition corrects endothelial dysfunction in cirrhotic rat livers."xsd:string
http://purl.uniprot.org/citations/12971960http://purl.uniprot.org/core/volume"39"xsd:string
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