Vascular endothelial growth factor's participation in splanchnic hyperdynamic circulation in portal hypertension
10.3760/cma.j.issn.1007-8118.2013.08.015
- VernacularTitle:血管内皮生长因子参与门静脉高压症内脏高动力循环
- Author:
Quanbo ZHOU
;
Min ZHANG
;
Wei CHEN
;
Jun QIN
;
Qing XU
;
Hong ZHOU
;
Meng LUO
- Publication Type:Journal Article
- Keywords:
Hypertension,portal;
Splanchnic circulation;
Vascular endothelial growth factors
- From:
Chinese Journal of Hepatobiliary Surgery
2013;19(8):611-616
- CountryChina
- Language:Chinese
-
Abstract:
Objective To detect the variation of vascular endothelial growth factor (VEGF) in the splanchnic vessels under portal hypertension (PHT) and explore its mechanism and influence on the process of hyperdynamic circulation.Methods In humans,the level of VEGF pathway related proteins were detected in the splenic artery of PHT patients in clinical trials.In animal experiments,the following parameters were observed for rats in the control group (group N,n =7) and the CCl4 induced portal hypertension group (group PHT,n=7):portal vein diameter,portal vein blood flow velocity (PBV),portal vein blood flow (PBF),portal vein pressure (PP),norepinephrine (NE) reactivity in the isolated mesenteric artery microcirculation,contractile reactivity and degree of endothelial ni tric oxide synthase (eNOS) activation in the mesenteric artery by selectively inhibiting the VEGF signal pathway with SU5416.In cell experiments,primary culturing of arterial endothelial cells in vitro were used to verify the effects of VEGF on eNOS activation.Results The results showed that VEGF expression levels in the splenic artery of PHT patients significantly increased.In animal experiments,there was not a significant difference in portal vein diameter between group N and group PHT.How ever,the PBV and PBF of group PHT were lower than those of group N,and SU5416 had no clear effect on PBV and PBF in group PHT.PP of group PHT was much higher than that of group N,and SU5416 had little influence on reducing PP in group PHT.The contractile response of mesenteric artery microcirculation to NE in group PHT decreased significantly,EC50 increased a lot,and SU5416 improved this hypoergia partially.The protein levels of VEGF,VEGFR-2,eNOS,and p-eNOS in the mesentery artery of group PHT raised quite a lot compared to group N,and SU5416 decreased the protein level of VEGFR-2 and activation of eNOS significantly.Experiments in vitro confirmed that VEGF could promote the activation of eNOS.Conclusion The excessive VEGF produced in visceral arteries under PHT may participate in the process of hyperdynamic circulation partially through promoting the synthesis and activation of eNOS and then reducing visceral arteries' response to NE.
