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LIVER AND BILIARY TRACT

Altered mesenteric venous capacitance and volume pooling in cirrhotic rats are mediated by nitric oxide

¹Liver Unit, Gastrointestinal Research Group and ²Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, Canada

Submitted 24 September 2007 ; accepted in final form 4 June 2008

In cirrhosis, despite augmented blood volume, effective circulating volume is decreased. This implies abnormal regulation of blood volume, i.e., venous pooling. Because gut veins are the main blood reservoir, we studied mesenteric venous capacitance and compliance in a rat model of cirrhosis. Cirrhosis was induced by bile duct ligation (4 wk). Controls were sham operated. Changes in first-order mesenteric vein diameters induced by drugs, hemorrhage, and stepwise increases in portal pressure (inflatable cuff) were directly observed by intravital microscopy. Effects of nitric oxide on responses to acute graded hemorrhage were studied by use of selective NO synthase (NOS) isoform inhibitors. Pressures were related to diameters to assess capacitance and compliance. Compared with controls, cirrhotic rats demonstrated increased mesenteric venous capacitance and decreased compliance. Norepinephrine induced venoconstriction but did not affect compliance. Prazosin markedly diminished compliance in controls but not cirrhotics. Conversely, the nonspecific NOS inhibitor N-nitro-L-arginine methyl ester (L-NAME) decreased compliance in cirrhotics, but not controls. Tetrodotoxin venodilated controls, venoconstricted cirrhotics, and markedly decreased compliance in both groups. When hemorrhaged, controls rapidly venoconstricted to compensate for initial hypotension, whereas cirrhotic rats remained hypotensive because venoconstriction was severely blunted. Pretreatment with L-NAME or the selective neuronal NOS inhibitors S-methyl-L-thiocitrulline and 7-nitroindazole normalized the homeostatic responses of cirrhotic rats, whereas the selective endothelial-constitutive NOS inhibitor N-iminoethyl-L-ornithine did not affect the response. In conclusion, mesenteric veins of cirrhotic rats showed enhanced capacitance, attenuated compensatory constrictive response to hemorrhage, and decreased compliance. The first two abnormalities were caused by neuronal NOS-derived nitric oxide.

blood volume; venous compliance; neuronal nitric oxide synthase; decreased effective circulating volume

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