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Liver Int. 2011 Jul;31(6):881-90. doi: 10.1111/j.1478-3231.2011.02509.x. Epub 2011 Mar 21.

Increased myoendothelial gap junctions mediate the enhanced response to epoxyeicosatrienoic acid and acetylcholine in mesenteric arterial vessels of cirrhotic rats.

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  • 1Department of Clinical and Experimental Medicine, University of Padua, Padua, Italy.



Cirrhotic portal hypertension is characterized by mesenteric arterial vasodilation and hyporeactivity to vasoconstrictors.


We evaluated the role of epoxyeicosatrienoic acid (EET) and of myoendothelial gap junctions (GJ) in the haemodynamic alterations of experimental cirrhosis.


Thirty-five control rats and 35 rats with carbon tetrachloride (CCl(4))-induced cirrhosis were studied. Small resistance mesenteric arteries (diameter <350 μm) were connected to a pressure servo controller in a video-monitored perfusion system. Concentration-response curves to acetylcholine (ACh) were evaluated in mesenteric arteries pre-incubated with indomethacin, N(G)-nitro-L-arginine-methyl-ester and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one before and after the epoxygenase inhibitor miconazole or 18α-glycyrrhetinic acid (18α-GA) (GJ inhibitor). EC(50) was calculated. Concentration-response curves to 11,12-EET were also evaluated. mRNA and protein expression of connexins (Cxs) in the mesenteric arteries was evaluated by real-time PCR and immunohistochemistry.


The ACh response was increased in cirrhotic rats (EC(50): -6.55±0.10 vs. -6.01±0.10 log[M]; P<0.01) and was blunted by miconazole only in cirrhotic animals. 18α-GA blunted the response to ACh more in cirrhotic than that in control rats (P<0.05). Concentration-response curves to 11,12-EET showed an increased endothelium-dependent vasodilating response in cirrhotic rats (P<0.05); the BK(Ca) inhibitor Iberiotoxin (25 nM) blocked the response in normal rats but not in cirrhotic rats, while 18α-GA blunted the response in cirrhotic rats but not in control rats. An increased mRNA and protein expression of Cx40 and Cx43 in cirrhotic arteries was detected (P<0.05).


The increased nitric oxide/PGI(2)-independent vasodilation of mesenteric arterial circulation in cirrhosis is because of, at least in part, hyperreactivity to 11,12-EET through an increased expression of myoendothelial GJs.

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