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Dysbalance in sympathetic neurotransmitter release and action in cirrhotic rats: Impact of exogenous Neuropeptide Y.
MedLine Citation:
PMID:  23041305     Owner:  NLM     Status:  Publisher    
BACKGROUND & AIMS: Splanchnic vasodilation is an essential disturbance in portal hypertension. Increased systemic sympathetic-nerve-activity is well-known, but potential corresponding vascular desensitization is characterized incompletely. 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 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 pressure-response to PNS, representing degree of desensitization, was enhanced in portal hypertension. NA-release was elevated, whereas NPY-release was attenuated in cirrhosis. Administration of exogenous NPY lead 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 portal hypertensive mesenteric vasculature revealing post- and prejunctional effects at the vascular-smooth-muscle motor-endplate; therefore outlining encouraging therapeutic strategies.
P Dietrich; L Moleda; F Kees; M Müller; R H Straub; C Hellerbrand; R Wiest
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-4
Journal Detail:
Title:  Journal of hepatology     Volume:  -     ISSN:  1600-0641     ISO Abbreviation:  J. Hepatol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8503886     Medline TA:  J Hepatol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier B.V.
Dept. Internal Medicine, University Medical Center, Regensburg, 93042, Germany.
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