title: Mesenteric arteries responsiveness to acute variations of wall shear stress is impaired in rats with liver cirrhosis.
abstract: OBJECTIVE
  In liver cirrhosis, excessive splanchnic vasodilation is due to abnormal synthesis of endogenous vasodilators and to decreased sensitivity to vasoconstrictors. The role of mechanical stimuli such as wall shear stress (WSS) on splanchnic circulation remains unclear. The aim of this study was to assess the vasodilation induced by wall shear stress (WSS) and acute changes in blood flow in the mesenteric arteries in an experimental model of liver cirrhosis.
  
  
  METHODS
  The effect of acute changes in intraluminal flow (0, 10, and 20 μl/min) and WSS on the diameter of the mesenteric arteries (diameters <500 μm) of control and cirrhotic rats was assessed, at baseline and after the inhibition of nitric oxide synthase, cyclooxygenase and hemeoxygenase. Concentration-response curves to phenylephrine were also obtained.
  
  
  RESULTS
  In controls, the increase in intraluminal flow led to a significant increase in arterial diameter (p < 0.05), while WSS remained stable; the effect was maintained in vessels pre-constricted with phenylephrine, blocked by the exposure to indomethacin and L-NAME and restored by the subsequent addition of chromium mesoporphyrin (p < 0.05). In cirrhotic arteries, arterial diameters did not change in response to acute increase in flow, neither at baseline nor after exposure to indomethacin and L-NAME, while WSS increased (p < 0.01). Responsiveness to flow was partially restored (p < 0.05) after exposure of the arteries to chromium mesoporphyrin in addition to indomethacin and L-NAME.
  
  
  CONCLUSIONS
  Arteries from cirrhotic rats showed an abolished responsiveness to acute variations in flow, which exposes the mesenteric endothelium to sudden variations in WSS.
authors: Clinica Medica 5, Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy. annalaurapiva@libero.it
authors: Anna
authors: A
authors: Piva
authors: Francesca
authors: F
authors: Zampieri
authors: Marco
authors: M
authors: Di Pascoli
authors: Angelo
authors: A
authors: Gatta
authors: David
authors: D
authors: Sacerdoti
authors: Massimo
authors: M
authors: Bolognesi
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors; D007213:Indomethacin / Q000494:pharmacology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology*; D008652:Mesoporphyrins / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000502:physiology; D013152:Splanchnic Circulation / Q000502:physiology*; D018709:Statistics, Nonparametric; D013314:Stress, Mechanical; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D008652:Mesoporphyrins; D014662:Vasoconstrictor Agents; C427471:chromium mesoporphyrin; D010656:Phenylephrine; D002251:Carbon Tetrachloride; D019001:Nitric Oxide Synthase; D006419:Heme Oxygenase (Decyclizing); D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin