The Relationship Of Heat Shock Protein 90 And Hyperdynamic Circulation In Cirrhotic Rats

Objective:By examining the expression and localization of Hsp90 andeNOS in mesenteric vasculature of cirrhosis rat , and determiningwether17-AAG can change the activity of eNOS and NO production,to test thefunctional link between eNOS activition and Hsp90 signaling and the role ofHsp90 in hyperdynamic circulation. Methods:Immunohistochemistry used to examined the expression andlocalization of Hsp90 and eNOS in mesenteric vasculature.The activity of eNOSwas detected by spectrophotometry,NO production was detected by method ofNitrate reductase. Statistical analysis was performed using two-sample t-test andANOVA. Results:Both eNOS and Hsp90 are expressed abundantly in the endotheliallining of mesenteric vessels as demonstrated by Immunohistochemistry.AlthougheNOS staining occurs exclusively within vascular endothelium, immunostaining for Hsp90is also demonstrated in mesenteric smooth muscle cells. The activity of eNOS and NOproduction was higher in cirrhotic rats compared with sham animals. 17-AAGcan attenuate signifitly the activity of eNOS and inhibit NO production. Conclusion:The interaction of eNOS with Hsp90 facilitates eNOS activityand NO production in the mesenteric vasculature of cirrhosis rat. This suggest thatHsp90 participates as a regulator of endothelial cell signal transduction leading to eNOSactivation and vasorelaxation. We demonstrated that Hsp90 play a key role inNO-dependent hyperdynamic circulation in portal hypertensive rats andprovides a novel method for future treatment of portal hypertension.