Heat shock protein 90 is responsible for hyperdynamic circulation in portal hypertensive rats

AIM: To examine the participation of HSP90 in portal hypertensive rat mesentery in vitro. METHODS: Immunohistochemistry and Western-blot were used to examine the expression of HSP90 in mesenteric vasculature. HSP90 mRNA was detected by RT-PCR, and the role of HSP90 in hyperdynamic circulation was examined by in vitro mesenteric perfusion studies. RESULTS: HSP90 was overexpressed in endothelium of mesentery vasculature in animals with experimental portal hypertension induced by partial portal vein ligation (PVL) compared with normal animals. Geldanamycin (GA), a special inhibitor of HSP90 signaling, attenuated ACh-dependent vasodilation but did not affect vasodilation in response to sodium nitroprusside in normal rats. In PVL animals, the perfused mesentery was hyporesponsive to vasoconstrictor methoxamine. GA significantly potentiated methoxamine-induced vasoconstrictor after PVL. CONCLUSION: HSP90 plays a key role in NO-dependent hyperdynamic circulation in portal hypertension and provides a novel method for future treatment of portal hypertension.