title: Prostacyclin decreases splanchnic vascular contractility in cirrhotic rats.
abstract: BACKGROUND
  Prostacyclin has been shown to increase portal hypertension, but the mechanism is unclear. This study aimed to investigate whether the overproduction of prostacyclin (PGI2) in cirrhosis participates in the splanchnic vascular hyporesponsiveness to vasoconstrictors in cirrhotic rats.
  
  
  METHODS
  Cirrhotic model was created by subcutaneous injection of 60% carbon tetrachloride (CCl4) corn oil solution combined with intermittent drinking of 5% alcohol, and age-matched rats served as controls. The isolated third-generation mesenteric arterioles were used to examine the contractile response to norepinephrine. The changes in vascular diameter were observed under a microscope imaging device. The plasma concentration of 6-ketone-prostaglandin F1alpha (6-keto-PGF1alpha, a stable metabolite of PGI2) was tested via enzyme immunoassays and the expression of cyclooxygenase (COX) in mesenteric arteries was detected by Western blotting.
  
  
  RESULTS
  In parallel with the increase of plasma 6-keto-PGF1alpha, the contractile response of arterioles from cirrhotic rats to norepinephrine was significantly impaired compared with that from controls. Inhibition of PGI2 or protein kinase A with indomethacin or Rp-adenosine 3', 5'-cyclic monophosphothioate (Rp-cAMPS) partially reversed the vascular hypo-contractile response to norepinephrine in arterioles from cirrhotic rats. Indomethacin significantly decreased the plasma 6-keto-PGF1alpha. Furthermore, indomethacin significantly attenuated the effect of Rp-cAMPS on arterioles from cirrhotic rats. COX-1 expression was up-regulated in mesenteric arteries from cirrhotic rats, whereas COX-2 was not detectable in the mesenteric arteries from both cirrhotic and control rats.
  
  
  CONCLUSIONS
  Enhanced COX-1 expression in cirrhotic rats resulted in elevated PGI2 production which partially contributed to the splanchnic vascular hyporesponsiveness to a vasoconstrictor via the protein kinase A pathway.
authors.affiliation: Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China. syw0616@126.com.
authors.forename: De-Jun
authors.initials: DJ
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Yan-Miao
authors.initials: YM
authors.lastname: Huo
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Zhang
authors.forename: Rong
authors.initials: R
authors.lastname: Hua
authors.forename: Yong-Wei
authors.initials: YW
authors.lastname: Sun
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001160:Arterioles / Q000378:metabolism / Q000503:physiopathology; D002251:Carbon Tetrachloride; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000097:blood / Q000378:metabolism*; D000431:Ethanol; D008104:Liver Cirrhosis, Alcoholic / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013152:Splanchnic Circulation / Q000187:drug effects; D015854:Up-Regulation; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; D047428:Protein Kinase Inhibitors; D014662:Vasoconstrictor Agents; D000431:Ethanol; D015121:6-Ketoprostaglandin F1 alpha; D002251:Carbon Tetrachloride; D011464:Epoprostenol; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; C489691:Ptgs2 protein, rat; D017868:Cyclic AMP-Dependent Protein Kinases