title: Dysbalance in sympathetic neurotransmitter release and action in cirrhotic rats: impact of exogenous neuropeptide Y.
abstract: OBJECTIVE
  Splanchnic vasodilation is an essential disturbance in portal hypertension. Increased systemic sympathetic nerve activity is well known, but potential corresponding vascular desensitization is incompletely characterized. Release of splanchnic sympathetic neurotransmitters noradrenaline (NA) and co-transmitter neuropeptide Y (NPY) remains to be elucidated. Finally, the effects of exogenous NPY on these mechanisms are unexplored.
  
  
  METHODS
  Portal vein ligated cirrhotic, and control rats were used for in vitro perfusion of mesenteric arteries. Depletion of vascular pressure response was induced by repetitive electric sympathetic perivascular nerve stimulation (PNS) and performed in the absence and presence of exogenous NPY. Additionally, PNS-induced release of NA and NPY was measured.
  
  
  RESULTS
  Mesenteric PNS-induced pressure response was lower in portal hypertension. Depletion of the pressure response to PNS, representing the degree of desensitization, was enhanced in portal hypertension. NA release was elevated, whereas NPY release was attenuated in cirrhosis. Administration of exogenous NPY led to marked recovery from desensitization and vasoconstrictive improvement in cirrhotic rats, being associated with more pronounced decrease of NA release.
  
  
  CONCLUSIONS
  Pronounced depletion of splanchnic arterial pressure-response to repetitive sympathetic nerve stimulation in cirrhosis is partly attributable to altered NA release as well as to deficient NPY release. External NPY restores vascular contractility and attenuates pathologically elevated NA release in the portal hypertensive mesenteric vasculature, revealing post-, and prejunctional effects at the vascular smooth muscle motor endplate; therefore outlining encouraging therapeutic strategies.
authors.affiliation: Dept. Internal Medicine, University Medical Center, Regensburg 93042, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Dietrich
authors.forename: L
authors.initials: L
authors.lastname: Moleda
authors.forename: F
authors.initials: F
authors.lastname: Kees
authors.forename: M
authors.initials: M
authors.lastname: Müller
authors.forename: R H
authors.initials: RH
authors.lastname: Straub
authors.forename: C
authors.initials: C
authors.lastname: Hellerbrand
authors.forename: R
authors.initials: R
authors.lastname: Wiest
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000009:adverse effects; D004195:Disease Models, Animal; D004558:Electric Stimulation; D006975:Hypertension, Portal / Q000378:metabolism / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009478:Neuropeptide Y / Q000378:metabolism / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D009478:Neuropeptide Y; D018377:Neurotransmitter Agents; D002251:Carbon Tetrachloride; D009638:Norepinephrine