Up-regulation of nNOS and associated increase in nitrergic vasodilation in superior mesenteric arteries in pre-hepatic portal hypertension

Jurzik, Lars and Froh, Matthias and Straub, Rainer H. and Schoelmerich, Juergen and Wiest, Reiner (2005) Up-regulation of nNOS and associated increase in nitrergic vasodilation in superior mesenteric arteries in pre-hepatic portal hypertension. JOURNAL OF HEPATOLOGY, 43 (2). pp. 258-265. ISSN 0168-8278, 1600-0641

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Abstract

Background/Aims: Splanchnic arterial vasodilation in portal hypertension has been attributed largely to vascular NO overproduction. Three NO-synthase (NOS) isoforms have been identified of which e(ndothelial)-NOS has been found up-regulated and i(nducible)-NOS not expressed in the splanchnic circulation in portal hypertension. So far, n(euronal)-NOS has not been investigated and hence, the current study evaluates nNOS-expression and nNOS-mediated vasorelaxation in a model of portal vein-ligated rats (PVL). Methods: Mesenteric vasculature of PVL and sham rats was evaluated for nNOS-protein (immunohistochemically and Western blotting). In vitro perfused de-endothelialized mesenteric arterial vasculature was pre-constricted with norepinephrine (EC80) and tested for nNOS-mediated vasorelaxation by periarterial nerve stimulation (PNS, 2-12 Hz, 45 V) before and after incubation with the NOS-inhibitor L-NAME (10(-4) M). Results: nNOS was localized to the adventitia of the mesenteric arterial tree showing more intense staining and increased protein expression in PVL as compared to sham rats. PNS induced a frequency-dependent vasorelaxation, which was more pronounced in PVL rats. L-NAME abolished this difference in nerval-mediated vasorelaxation, the effect being significantly greater in PVL than in sham animals. Conclusions: Perivascular nNOS-protein expression is enhanced in mesenteric arteries in portal hypertension mediating an increased nerval NO-mediated vasorelaxation. This nNOS-derived NO overproduction may play an important role in the pathogenesis of arterial vasodilation in portal hypertension. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Item Type: Article
Uncontrolled Keywords: NITRIC-OXIDE SYNTHASE; CIRRHOTIC RATS; HYPERDYNAMIC CIRCULATION; BACTERIAL TRANSLOCATION; SPLANCHNIC CIRCULATION; CEREBRAL-ARTERIES; NERVOUS-SYSTEM; RENAL SODIUM; VESSELS; RELAXATION; nitric oxide; vasodilation; portal hypertension; mesenteric circulation
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin I
Depositing User: Dr. Gernot Deinzer
Date Deposited: 03 May 2021 08:24
Last Modified: 03 May 2021 08:24
URI: https://pred.uni-regensburg.de/id/eprint/35820

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