Hepatic venous dysregulation contributes to blood volume pooling in cirrhotic rats

Yang Li ¹, Hongqun Liu ¹, Seyed Ali Gaskari ¹, Donna Marie McCafferty ² and Samuel S. Lee ^1*

¹ Liver Unit, University of Calgary, Canada
² GI Research Group, University of Calgary, Canada

^* To whom correspondence should be addressed. E-mail: samlee{at}ucalgary.ca.

Accepted 22 December 2005

Abstract

Background/aims: In cirrhosis, despite increased total blood volume, the circulation behaves as if it were volume-depleted, a phenomenon termed "decreased effective circulating volume". As the gut/liver veins are the major blood reservoir, this suggests hepatosplanchnic venous pooling. We therefore aimed to elucidate the vasoactive responses of the hepatic veins in cirrhosis.

Methods: Cirrhosis was induced by chronic bile duct ligation in rats. The in vivo responses of postsinusoidal venules and sinusoids to vasoactive drugs, 20% hemorrhage and 20% mannitol (volume expansion) were examined by intravital microscopy. In isolated perfused livers, change in liver weight was measured as an index of the hepatic vascular volume response.

Results: Blood volume was significantly increased in cirrhotic rats. In cirrhotic hepatic vasculature, constrictive responses to norepinephrine and hemorrhage were blunted compared to controls. In contrast, the dilatory responses to the NO donor sodium nitroprusside and volume expansion were enhanced. Both constrictive and dilatory abnormalities were reversed by the NO synthase inhibitor L-NAME.

Conclusions: The hepatic sinusoidal and venous bed of cirrhotic rats showed an enhanced dilatory capacity to buffer volume increases but inadequately constricted in response to volume depletion or catecholamines. Both abnormalities may contribute to volume pooling and are mediated by nitric oxide.

Keywords: cirrhosis, intravital microscopy, nitric oxide, postsinusoidal venule, sinusoid

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Relevant Article

Digest

Robin Spiller and Alastair Watson
Gut 2006 55: 905. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

• Moezi, L., Gaskari, S. A., Lee, S. S. (2008). Endocannabinoids and Liver Disease. V. Endocannabinoids as mediators of vascular and cardiac abnormalities in cirrhosis. Am. J. Physiol. Gastrointest. Liver Physiol. 295: G649-G653 [Abstract] [Full Text]  
• Li, Y., Liu, H., Gaskari, S. A., Tyberg, J. V., Lee, S. S. (2008). Altered mesenteric venous capacitance and volume pooling in cirrhotic rats are mediated by nitric oxide. Am. J. Physiol. Gastrointest. Liver Physiol. 295: G252-G259 [Abstract] [Full Text]