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Cyclooxygenase-derived products modulate the increased intrahepatic resistance of cirrhotic rat livers.
Hepatology. 2003 Jan; 37(1):172-81.Hep

Abstract

In cirrhotic livers, increased resistance to portal flow, in part due to an exaggerated response to vasoconstrictors, is the primary factor in the pathophysiology of portal hypertension. Our aim was to evaluate the response of the intrahepatic circulation of cirrhotic rat livers to the alpha(1)-adrenergic vasoconstrictor methoxamine and the mechanisms involved in its regulation. A portal perfusion pressure dose-response curve to methoxamine was performed in control and cirrhotic rat livers preincubated with vehicle, the nitric oxide synthase blocker N(G)-nitro-L-arginine (L-NNA), indomethacin cyclooxygenase (COX) inhibitor, L-NNA + indomethacin, or the thromboxane (TX) A(2) receptor blocker SQ 29,548. TXA(2) production, COX-1 and COX-2 mRNA expression, and immunostaining for TXA(2) synthase were evaluated. Cirrhotic livers exhibited a hyperresponse to methoxamine associated with overexpression of COX-2 and TXA(2) synthase as well as with increased production of TXA(2). The hyperresponse to methoxamine of cirrhotic livers disappeared by COX inhibition with indomethacin but not after NO inhibition. SQ 29,548 also corrected the hyperresponse of cirrhotic livers to methoxamine. In conclusion, COX-derived prostanoids, mainly TXA(2), play a major role in regulating the response of cirrhotic livers to methoxamine.

Authors+Show Affiliations

Graupera M
Hepatic Hemodynamic Laboratory, Liver Unit, Institut Malalties Digestives, University of Barcelona, Spain.
García-Pagán JC
No affiliation info available
Abraldes JG
No affiliation info available
Peralta C
No affiliation info available
Bragulat M
No affiliation info available
Corominola H
No affiliation info available
Bosch J
No affiliation info available
Rodés J
No affiliation info available

MeSH

6-Ketoprostaglandin F1 alphaAdrenergic alpha-AgonistsAnimalsArachidonic AcidBlood PressureCarbon TetrachlorideCyclooxygenase 1Cyclooxygenase 2Cyclooxygenase 2 InhibitorsCyclooxygenase InhibitorsDinoprostIsoenzymesLiver CirculationLiver CirrhosisMaleMembrane ProteinsMethoxamineNitric OxidePortal SystemProstaglandin-Endoperoxide SynthasesRNA, MessengerRatsRats, WistarReceptors, ThromboxaneThromboxane A2Vascular Resistance

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12500202

Citation

Graupera, Mariona, et al. "Cyclooxygenase-derived Products Modulate the Increased Intrahepatic Resistance of Cirrhotic Rat Livers." Hepatology (Baltimore, Md.), vol. 37, no. 1, 2003, pp. 172-81.
Graupera M, García-Pagán JC, Abraldes JG, et al. Cyclooxygenase-derived products modulate the increased intrahepatic resistance of cirrhotic rat livers. Hepatology. 2003;37(1):172-81.
Graupera, M., García-Pagán, J. C., Abraldes, J. G., Peralta, C., Bragulat, M., Corominola, H., Bosch, J., & Rodés, J. (2003). Cyclooxygenase-derived products modulate the increased intrahepatic resistance of cirrhotic rat livers. Hepatology (Baltimore, Md.), 37(1), 172-81.
Graupera M, et al. Cyclooxygenase-derived Products Modulate the Increased Intrahepatic Resistance of Cirrhotic Rat Livers. Hepatology. 2003;37(1):172-81. PubMed PMID: 12500202.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cyclooxygenase-derived products modulate the increased intrahepatic resistance of cirrhotic rat livers. AU - Graupera,Mariona, AU - García-Pagán,Joan-Carles, AU - Abraldes,Juan G, AU - Peralta,Carmen, AU - Bragulat,Mireia, AU - Corominola,Helena, AU - Bosch,Jaume, AU - Rodés,Juan, PY - 2002/12/25/pubmed PY - 2003/1/24/medline PY - 2002/12/25/entrez SP - 172 EP - 81 JF - Hepatology (Baltimore, Md.) JO - Hepatology VL - 37 IS - 1 N2 - In cirrhotic livers, increased resistance to portal flow, in part due to an exaggerated response to vasoconstrictors, is the primary factor in the pathophysiology of portal hypertension. Our aim was to evaluate the response of the intrahepatic circulation of cirrhotic rat livers to the alpha(1)-adrenergic vasoconstrictor methoxamine and the mechanisms involved in its regulation. A portal perfusion pressure dose-response curve to methoxamine was performed in control and cirrhotic rat livers preincubated with vehicle, the nitric oxide synthase blocker N(G)-nitro-L-arginine (L-NNA), indomethacin cyclooxygenase (COX) inhibitor, L-NNA + indomethacin, or the thromboxane (TX) A(2) receptor blocker SQ 29,548. TXA(2) production, COX-1 and COX-2 mRNA expression, and immunostaining for TXA(2) synthase were evaluated. Cirrhotic livers exhibited a hyperresponse to methoxamine associated with overexpression of COX-2 and TXA(2) synthase as well as with increased production of TXA(2). The hyperresponse to methoxamine of cirrhotic livers disappeared by COX inhibition with indomethacin but not after NO inhibition. SQ 29,548 also corrected the hyperresponse of cirrhotic livers to methoxamine. In conclusion, COX-derived prostanoids, mainly TXA(2), play a major role in regulating the response of cirrhotic livers to methoxamine. SN - 0270-9139 UR - https://www.unboundmedicine.com/medline/citation/12500202/Cyclooxygenase_derived_products_modulate_the_increased_intrahepatic_resistance_of_cirrhotic_rat_livers_ DB - PRIME DP - Unbound Medicine ER -