Basic–liver, pancreas, and biliary tractEvidence Against a Role for NADPH Oxidase Modulating Hepatic Vascular Tone in Cirrhosis
Section snippets
Induction of Cirrhosis by CCl4
Male Wistar rats weighing 175–200 g underwent inhalation exposure to CCl4 and received phenobarbital in the drinking water as previously described.16 Once the cirrhotic rats developed ascites, administration of CCl4 and phenobarbital was stopped and experimental protocols were started 1 week later. Control animals received only phenobarbital. The animals were kept in environmentally controlled animal facilities at the Institut d’Investigacions Biomèdiques August Pi i Sunyer. Here and in the
NADPH Oxidase mRNA Expression
Control and cirrhotic rat livers expressed NOX2, NOX4, p22phox, p47phox, and p67phox mRNA but not NOX1 mRNA. The levels of NOX2, p22phox, p47phox, and p67phox mRNA were significantly increased, but NOX4 mRNA levels were significantly reduced in cirrhotic in comparison with control livers (Figure 1).
By contrast, expression of the mRNA NOX1 subunit was almost undetectable, both in control and in cirrhotic livers. Indeed, the expression was about 200 times lower than those observed in mRNA from
Discussion
Increased hepatic vascular resistance in cirrhosis has been related to reduced NO bioavailability within the cirrhotic liver,2, 6, 24 mainly attributed to reduced endothelial nitric oxide synthase activity.2, 6, 24, 25 It has been recently proposed that, in analogy with other vascular disorders,7, 8, 9 the reduced NO bioavailability in the cirrhotic liver would be further aggravated by NO scavenging due to its binding to superoxide, which is increased in several liver disorders.10, 12, 13, 14,
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J.G.S. has a fellowship from Instituto de Salud Carlos III (FI05/00133). This study was supported by grants from the Ministerio de Educación y Ciencia (SAF 04/04783) and Instituto de Salud Carlos III (PI04-0665 and PI06-0623).