The effects and mechanisms of vitamin C on intestional mesenteric arterioles responsiveness to vasoconstrictors in patients with cirrhosis and portal hypertension

Abstract

Objective To study the changes of mesenteric arterioles on the contractile response to norepinephrine in patients with cirrhosis and portal hypertension (PHT) caused by hepatitis B after treatment by high-dose vitamin C.Methods Eleven PHT patients and 6 non-PHT volunteer were those undergoing their respective surgeriesat in our hospital from January 2010 to June 2011.The PHT patients were randomly assigned to vitamin C treatment group and placebo treatment group.After admission and before induction of anesthesia,blood taken to mesure plasma concentration of malonaldehyde (MDA).Intraoperative portal pressure was measured.We took the third level intestinal mesentery vessels with their mesentery next to the jejunum and studied the contractile response to norepinephrine of the intestinal mesenteric arterioles.We also measured RhoA/ROCK pathway associated proteins' expression and activity changes by Western-blot method.Results The average value of the plasma MDA of PHT patients with cirrhosis was much higher than that of non-PHT patients.After treatment by vitamin C,the value decreased.The dose-response curve of isolated mesenteric arterioles to norepinephrine from PHT patients with cirrhosis shifted to the right,and the EC50 value was higher than that of non-PHT patients.But this phenomenon was reversed after the patients treated with vitamin C.The protein expression of RhoA in mesenteric arteries did not change significantly among the three groups.But the protein expression and activity of ROCK-1 was significantly reduced in PHT patients with cirrhosis.After treatment with vitamin C,the expression and activity of ROCK-1 in mesenteric arteries of cirrhosis was significantly increased.Conclusion The PHT patients with cirrhosis are in the situation of oxidative stress.The high-dose vitamin C treatment can reduce oxidative stress level and improve contractile hyporeactivity of mesenteric arterioles of PHT patients with cirrhosis to norepinephrine.The protein expression and activity increasement of ROCK in RhoA/ ROCK pathway is involved in thisphenomenon. Key words: Hypertension, portal; Mesentric arteries ; Ascorbic acid ; Malonaldehyde