title: Vasoconstrictor responses are normal but prostanoid-mediated vasodilatation is enhanced in human cirrhotic mesenteric arteries.
abstract: OBJECTIVE
  The mechanisms responsible for mesenteric vasodilatation in cirrhosis have not been fully elucidated. The aim of the present study was to examine whether there is altered intrinsic vascular reactivity of human mesenteric vessels in cirrhosis, which might contribute to vasodilatation in vivo.
  
  
  METHODS
  Ten mesenteric arteries from six cirrhosis patients undergoing liver transplantation were compared with 11 arteries from six control patients. Vasoconstrictor responses to potassium, norepinephrine and methoxamine were determined. Endothelium-dependent vasodilatation responses to acetylcholine and substance P were determined both before and after inhibition of nitric oxide (NO) and prostanoid synthesis.
  
  
  RESULTS
  Cirrhotic vessels responded normally to potassium depolarization and did not differ to control vessels with respect to sensitivity and maximal response to norepinephrine. In cirrhotic vessels, inhibition of NO synthesis had significantly less effect on substance P-induced vasorelaxation than in controls (% Relaxation: cirrhosis 70.3 +/- 9.6; control 34.9 +/- 9.5; P = 0.03). However, after inhibition of both NO and prostanoid synthesis, vasodilatory responses were eliminated in both groups.
  
  
  CONCLUSIONS
  The findings of the present study indicate that intrinsic hyporesponsiveness to vasoconstrictors does not play a pathogenetic role in the mesenteric vasodilatation in human cirrhosis. Furthermore, vasodilator prostanoids might make a significant contribution in mediating enhanced endothelium-dependent vasorelaxation in the mesenteric circulation.
authors.affiliation: Victorian Liver Transplant Unit, Department of Gastroenterology, Austin Health, Heidelberg, Melbourne, Victoria 3084, Australia.
authors.forename: Rhys B
authors.initials: RB
authors.lastname: Vaughan
authors.forename: James A
authors.initials: JA
authors.lastname: Angus
authors.forename: Peter W
authors.initials: PW
authors.lastname: Angus
mesh_terms: D002317:Cardiovascular Agents / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008103:Liver Cirrhosis / Q000503:physiopathology / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000473:pathology; D008875:Middle Aged; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D019335:Nitroarginine / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D002317:Cardiovascular Agents; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019335:Nitroarginine; D009569:Nitric Oxide; D007213:Indomethacin