Neural vasoregulation represents a rapid and potent mode of altering vascular tone but has not been investigated thoroughly during portal hypertension. Heat shock protein-90 (HSP-90) is well-known to act as a molecular chaperone optimizing endothelial and neural NO-synthase (eNOS, nNOS) enzyme activity and thus, NO production. Although HSP-90 has been shown to mediate in large parts the enhanced eNOS-dependent NO overproduction in the splanchnic circulation during portal hypertension, it is not clear what role HSP-90 plays in nNOS-mediated vasorelaxation in this scenario.
A research article to be published on April 21, 2010 in the World Journal of Gastroenterology addresses this question. This research relates to the utilization of the McGregor preparation enabling physiological and pharmacological testing of the whole mesenteric vasculature in its original anatomy and innervations. In contrast to arterial strips, this ensures testing of neural vasoregulation at close to in vivo conditions.
The investigators for the first time demonstrate a critical role of HSP-90 for nNOS-mediated vasorelaxation and furthermore, can provide evidence for this interaction being responsible in large parts for the well-accepted pronounced nNOS-dependent vasodilatation in portal hypertension. In addition, the authors visualize the localization of nNOS and HSP-90 in mesenteric nerves which can be appreciated as co-localized within the nerve axon. Finally, co-immunoprecipiatation reveals a close protein-protein-interaction explaining the functional hemodynamic results presented. Therefore, HSP-90 may well have great potential to be identified as a future target in clinical trials focusing on amelioration of portal hypertension and associated hemodynamic disturbances.
Reference: Moleda L, Jurzik L, Froh M, Gäbele E, Hellerbrand C, Straub RH, Schölmerich J, Wiest R. Role of HSP-90 for increased nNOS-mediated vasodilation in mesenteric arteries in portal hypertension. World J Gastroenterol 2010; 16(15): 1837-1844 http://www.wjgnet.com/1007-9327/full/v16/i15/1837.htm
Correspondence to: Reiner Wiest, MD, Department of Internal Medicine I, University Medical Center, D-93042 Regensburg, Germany. reiner.wiest@klinik.uni-regensburg.de
Telephone: +49-941-9447014 Fax: +49-941-9447016
About World Journal of Gastroenterology
World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection and provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2008 IF: 2.081. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.
Journal
World Journal of Gastroenterology