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The role of nitric oxide in the pathogenesis of systemic and splanchnic vasodilation in cirrhotic rats before and after the onset of ascites
Author(s) -
Angeli Paolo,
FernándezVaro Guillermo,
Dalla Libera Virna,
Fasolato Silvano,
Galioto Alessandra,
Arroyo Vicente,
Sticca Antonietta,
Guarda Silvia,
Gatta Angelo,
Jiménez Wladimiro
Publication year - 2005
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2005.01092.x
Subject(s) - splanchnic , ascites , cirrhosis , pathogenesis , medicine , vasodilation , hyperdynamic circulation , nitric oxide , endocrinology , portal hypertension , mesenteric arteries , nitric oxide synthase , vascular resistance , hemodynamics , artery
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 (Nω‐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.