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


CONCLUSIONS
HSP90 plays a key role in NO-dependent hyperdynamic circulation in portal hypertension and provides a novel method for future treatment of portal hypertension.
Ai
Jian-Hua
JH
Center for Hepatic Surgery, Tongi Hospital, Tongi Medical College, Huazhong Science and Technological University, Wuhan, Hubei Province, China. aijh_2000@yahoo.com
Yang
Zhen
Z
Qiu
Fa-Zu
FZ
Zhu
Tong
T
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D015870:Gene Expression; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics*; D006975:Hypertension, Portal / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D018841:HSP90 Heat-Shock Proteins; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D008729:Methoxamine; D000109:Acetylcholine