Experimental study of nitric oxide in decreasing intestinal mesenteric arterial hypocontractility in rats with hepatic cirrhosis and portal hypertension
10.3760/cma.j.issn.1673-9752.2013.03.015
- VernacularTitle:一氧化氮降低肝硬化门静脉高压症血管收缩反应性的实验研究
- Author:
Meng LUO
;
Wei CHEN
;
Jun QIN
;
Dejun LIU
;
Jianxia LIU
;
Lei QIN
;
Haixin QIAN
- Publication Type:Journal Article
- Keywords:
Liver cirrhosis;
Portal hypertension;
Nitric oxide
- From:Chinese Journal of Digestive Surgery
2013;(3):222-227
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanisms of nitric oxide (NO) in decreasing intestinal mesenteric arterial hypocontractility in rats with hepatic cirrhosis and portal hypertension,and to analyze the interaction of NO and RhoA/ROCK pathway.Methods The levels of NO in the peripheral blood and mesenteric artery of normal rats (normal control group,5 rats),rats with portal hypertension (experimental control group,6 rats)and rats with portal hypertension treated by L-NAME (L-NAME group,6 rats) were detected.Mesenteric arteriole contractility to norepinephrine in the 3 groups was determined using a vessel perfusion system.The expressions of proteins of NO-cGMP-PKG pathway and RhoA/ROCK pathway in the 3 groups were detected by Western blot.All data were analyzed using the analysis of variance or LSD-t test.The changes of mesenteric arteriole contractility to norepinephrine was expressed in dose-response curve,and was analyzed using the nonlinear regression method,and the EC50 value was calculated.Results (1) The pressures of portal veins of the normal control group,experimental control group and L-NAME group were (6.2 ± 0.9)mm Hg (1 mm Hg =0.133 kPa),(13.9 ± 1.7)mm Hg and (16.6 ± 1.3) mm Hg,respectively,with a significant difference among the 3 groups (F =94.4,P ＜ 0.05).(2) The levels of NO in the normal control group,experimental control group and L-NAME group were (43 ± 5) μmol/L,(82 ± 16) μmol/L and (45 ± 9) μmol/L,respectively,with a significant difference among the 3 groups (F =24.77,P ＜ 0.05).The level of NO of the L-NAME group was significantly lower than that of the experimental control group (P ＜ 0.05).(3) The levels of NO in the mesenteric artery of the normal control group,experimental control group and L-NAME group were (236 ±41) μmol/g,(407 ± 82) μmol/g and (216 ± 42) μmol/g,respectively,with a significant difference among the 3 groups (F =20.29,P ＜ 0.05).The NO level of the L-NAME group was significantly lower than that of the experimental control group (P ＜ 0.05).(4) Compared with the experimental control group,the dose-response curve of mesenteric arterioles to norepinephrine shifted to the left,while it did not reach the level of the normal control group.The levels of EC50 of the normal control group,experimental control group and the L-NAME group were 6.458 × 10-7 mol,9.546 × 10-7 mol and 7.494 × 10-7 mol,respectively.There was a significant difference in the EC50 level between the L-NAME group and the other two group (t =2.726,3.112,P ＜ 0.05).(5) Compared with the normal control group,the protein expression levels of eNOS and p-VASP of mesenteric artery of the experimental control group were significantly increased (P ＜ 0.05),while they were decreased in the L-NAME group (P ＜ 0.05).The protein expression levels of eNOS and p-VASP of mesenteric artery of the L-NAME group were significantly higher than those of the normal control group (P ＜0.05).There were no obvious changes of protein expression levels of PKG-1,ROCK-1 and p-moesin in the 3 groups (P ＞ 0.05).(6) The activity of ROCK-1 was significantly increased with norepinephrine stimulation in the normal control group and the L-NAME group,while no obvious changes were detected in the experimental control group.Conclusions The NO expression is upregulated in mesenteric arteries in rats with hepatic cirrhosis and portal hypertension.Such changes induce ROCK activation via influencing the expression of vasoconstrictors.L-NAME can reduce the NO levels in the mesenteric arteries,which may improve RhoA/ROCK signal pathway transduction.This can help vasoconstrictors induce ROCK activation without affecting the protein expression of ROCK.
