Moleda, Lukas and Jurzik, Lars and Froh, Matthias and Gaebele, Erwin and Hellerbrand, Claus and Straub, Rainer H. and Schoelmerich, Jurgen and Wiest, Reiner (2010) Role of HSP-90 for increased nNOS-mediated vasodilation in mesenteric arteries in portal hypertension. WORLD JOURNAL OF GASTROENTEROLOGY, 16 (15). pp. 1837-1844. ISSN 1007-9327, 2219-2840
Full text not available from this repository. (Request a copy)Abstract
AIM: To explore the role of heat shock protein-90 (HSP-90) for nitrergic vasorelaxation in the splanchnic circulation in rats with and without portal hypertension. METHODS: Neuronal nitric oxide synthase (nNOS) and HSP-90 were analyzed by immunofluorescence, western blotting and co-immunoprecipitation in the mesenteric vasculature and isolated nerves of portal-vein-ligated (PVL) rats and sham operated rats. In vitro perfused de-endothelialized mesenteric arterial vasculature was preconstricted with norepinephrine (EC80) and tested for nNOS-mediated vasorelaxation by periarterial nerve stimulation (PNS, 2-12 Hz, 45V) before and after incubation with geldanamycin (specific inhibitor of HSP-90 signalling, 3 mu g/mL) or L-NAME (non-specific NOS-blocker, 10(-4) mol/L). RESULTS: nNOS and HSP-90 expression was significantly increased in mesenteric nerves from PVL as compared to sham rats. Moreover, nNOS and HSP-90 were visualized in mesenteric nerves by immunofluorescence and immunoprecipitation of nNOS co-immunoprecitated HSP-90 in sham and PVL rats. PNS induced a frequency-dependent vasorelaxation which was more pronounced in PVL as compared to sham rats. L-NAME and geldanamycin markedly reduced nNOS-mediated vasorelaxation abrogating differences between the study groups. The effect of L-NAME and geldanamycin on nNOS-mediated vasorelaxation was significantly greater in PVL than in sham animals. However, no difference in magnitude of effect between L-NAME and geldanamycin was noted. CONCLUSION: HSP-90 acts as a signalling mediator of nNOS-dependent nerve mediated vascular responses in mesenteric arteries, and the increased nitrergic vasorelaxation observed in portal hypertension is mediated largely by HSP-90. (C) 2010 Baishideng. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NITRIC-OXIDE SYNTHASE; HSP90-BASED CHAPERONE SYSTEM; CIRRHOTIC RATS; HYPERDYNAMIC CIRCULATION; BACTERIAL TRANSLOCATION; SPLANCHNIC CIRCULATION; SIGNAL-TRANSDUCTION; IN-VIVO; HSP90; GELDANAMYCIN; Heat shock protein-90; 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 Aug 2020 06:04 |
| Last Modified: | 03 Aug 2020 06:04 |
| URI: | https://pred.uni-regensburg.de/id/eprint/24815 |
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