[Role of heat shock protein 90 in hyperdynamic circulation of portal hypertensive rats].
OBJECTIVE
To study the role of heat shock protein 90 (HSP 90) in the formation of hyperdynamic circulation of portal hypertensive rats.


METHODS
Animal model of portal hypertension was established by partial ligation of the portal vein among 20 SD rats (group P). Ten rats underwent sham operation (group S) Four weeks after the operation, the rats were killed and their mesenteric arteries and portal veins were obtained. The expression of HSP 90 in the portal veins and part of the superior mesenteric arteries was detected by Western blotting. Another mesenteric arteries underwent continuous perfusion with methoxamine (MTX, 30 and 100 micro mol/L) or acetylcholine (Ach). The perfusion pressure was monitored by a sensor. The concentration-response curves were examined in response to MTX and Ach infusion respectively. Then geldanamycin (GA) was infused; responses to MTX and ACh were repeated as described above. The endothelia of these arteries was denuded. After endothelial denudation was achieved, response to sodium nitroprusside (SNP) was examined.


RESULTS
The expression of HSP 90 was much stronger in the group P than in the group S. The perfusion pressure of the mesenteric artery of the group P was 13.32 mm Hg +/- 0.55 mm Hg, significantly lower than that of the group S (17.33 mm Hg +/- 0.57 mm Hg, n = 10, P < 0.001). After the addition of MTX, the perfusion pressure of the mesenteric artery of the group P was 141.9 mm Hg +/- 7.6 mm Hg, significantly lower than that of the group S (181.1 mm Hg +/- 16.2 mm Hg, n = 8, P < 0.001). GA and 30 micro mol/L or 100 micro mol/L MTX were added successively into the perfusion fluid for the mesenteric superior artery of the group P, then the perfusion pressure became 106.7 mm Hg +/- 7.5 mm Hg or 124.9 mm Hg +/- 5.5 mm Hg, significantly higher than those of the mesenteric superior artery of the group P without addition of GA (60.9 mm Hg +/- 4.3 mm Hg, n = 5, P < 0.05 and 98.7 mm Hg +/- 4.7 mm Hg, n = 5, P < 0.05). GA and 100 micro mol/L MTX were added successively into the perfusion fluid for the mesenteric superior artery of the group S, the perfusion pressure became 151.2 mm Hg +/- 7.1 mm Hg, not significantly different from that of the mesenteric superior artery of the group S without addition of GA (149.8 mm Hg +/- 5.6 mm Hg, P > 0.05). With the addition of GA in advance, the ACh-dependent vasorelaxation of the isolated perfused rat mesenteric artery was significantly attenuated in comparison with the mesenteric artery without addition of GA into whose perfusion fluid (P < 0.05). However, GA did not affect the vasodilation of the ensothelium-neduded mesenteric artery in response to SNP.


CONCLUSIONS
HSP90 is responsible for the hyperdynamic circulation in the portal hypertensive rats.
Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Jian-hua
JH
Ai
Zhen
Z
Yang
Fa-zu
FZ
Qiu
D000109:Acetylcholine / Q000627:therapeutic use; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D016227:Benzoquinones; D015153:Blotting, Western; D004195:Disease Models, Animal; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000097:blood*; D006975:Hypertension, Portal / Q000503:physiopathology*; D047029:Lactams, Macrocyclic; D008297:Male; D008729:Methoxamine / Q000627:therapeutic use; D011169:Portal Vein / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D011809:Quinones / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000627:therapeutic use; D014665:Vasodilator Agents / Q000627:therapeutic use
D000903:Antibiotics, Antineoplastic; D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D011809:Quinones; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D008729:Methoxamine; D000109:Acetylcholine; C001277:geldanamycin