The role of nitric oxide in the pathogenesis of systemic and splanchnic vasodilation in cirrhotic rats before and after the onset of ascites.

Abstract

BACKGROUND:

The role of nitric oxide (NO) in the pathogenesis of splanchnic arterial vasodilation in cirrhosis has been recently debated by some experimental studies.

AIMS:

We investigated the role of NO in the pathogenesis of the splanchnic arterial vasodilation along the course of CCl(4)-induced experimental cirrhosis.

METHODS:

We analyzed the effect on mean arterial pressure (MAP), cardiac output (CO), total peripheral resistance (TPR), and resistance in the superior mesenteric artery (RSMA), before and after the administration of a unspecific NO synthase (NOS) inhibitor (Nomega-nitro-L-arginine-methyl-ester, L-NAME) and a specific NOS2 inhibitor (L-N-(1-iminoethyl)-lysine, L-NIL) to cirrhotic rats with and without ascites, and to control rats. NOS2 and NOS3 protein expression was also assessed in systemic and splanchnic arteries of these animals.

RESULTS:

L-NAME in cirrhotic rats markedly improved MAP, and TPR and decreased CO regardless of whether they had ascites or not. L-NIL did not produce any significant effect on systemic haemodynamics in control and cirrhotic rats. NOS3 overexpression in the aorta of cirrhotic animals paralleled the progression of the liver disease. L-NAME increased RSMA in cirrhotic rats, but this effect was much less intense in rats with ascites. L-NIL had an effect only on RSMA in rats with ascites, which was of a similar extent to that produced by L-NAME. Western blot experiment showed a faint overexpression of NOS3 in the mesenteric artery of cirrhotic rats with and without ascites and a clear induction of NOS2 only in the mesenteric artery of rats with ascites.

CONCLUSIONS:

These results indicate that NO contributes significantly to the pathogenesis of arterial splanchnic circulation in the early stages of experimental cirrhosis but has only a minor role in its maintenance after the development of ascites. Furthermore, the expression of the different NOS isoforms varies along the course of the liver disease.

• Authors: Paolo Angeli, Guillermo Fernández-Varo, Virna Dalla Libera, Silvano Fasolato, Alessandra Galioto, Vicente Arroyo, Antonietta Sticca, Silvia Guarda, Angelo Gatta, Wladimiro Jiménez
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 25 Issue 2 Pg. 429-37 (Apr 2005) ISSN: 1478-3223 [Print] United States
• PMID: 15780069 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright Blackwell Munksgaard 2005

Chemical References

• Nitric Oxide Synthase
• NG-Nitroarginine Methyl Ester

Topics

• Analysis of Variance
• Animals
• Ascites (enzymology, physiopathology)
• Disease Models, Animal
• Hemodynamics (drug effects, physiology)
• Infusions, Intravenous
• Liver Cirrhosis, Experimental (enzymology, physiopathology)
• Male
• Mesenteric Arteries (drug effects, physiology)
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide Synthase (drug effects, metabolism)
• Probability
• Random Allocation
• Rats
• Rats, Wistar
• Sensitivity and Specificity
• Vascular Resistance
• Vasodilation (drug effects)