Dietrich, P. and Moleda, L. and Kees, F. and Mueller, M. and Straub, R. H. and Hellerbrand, C. and Wiest, R. (2013) Dysbalance in sympathetic neurotransmitter release and action in cirrhotic rats: Impact of exogenous neuropeptide Y. JOURNAL OF HEPATOLOGY, 58 (2). pp. 254-261. ISSN 0168-8278,
Full text not available from this repository. (Request a copy)Abstract
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 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. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SUPERIOR MESENTERIC-ARTERIES; PORTAL HYPERTENSIVE-RATS; DIPEPTIDYL PEPTIDASE-IV; NITRIC-OXIDE; HARBORING PHEOCHROMOCYTOMA; SPLANCHNIC VASODILATION; NERVE STIMULATION; RENAL-FUNCTION; VASCULAR-TONE; NORADRENALINE; Neuropeptide Y; Noradrenaline; Perivascular nerve-stimulation; Portal hypertension; Splanchnic circulation |
| Subjects: | 600 Technology > 610 Medical sciences Medicine 600 Technology > 615 Pharmacy |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Chemistry and Pharmacy > Institute of Pharmacy > Pharmacology and Toxicology (Prof. Schlossmann, formerly Prof. Seifert) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Apr 2020 12:29 |
| Last Modified: | 24 Apr 2020 12:29 |
| URI: | https://pred.uni-regensburg.de/id/eprint/17197 |
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