Obstructive jaundice activates nitroxidergic neurons of the vago-vagal neural circuit that regulates the hepatobiliary system in rabbits

Ming E. Hu, Yung Chang Lin, Hung Ming Chang, Yeu Sheng Tyan, Chyn Tair Lan

Research output: Contribution to journalArticle

Abstract

In this study, we investigated the expression of neuronal nitric oxide synthase (nNOS) and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d), two specific enzymes for nitric oxide (NO) synthesis, in the development of liver fibrosis induced by chronic bile duct ligation (BDL) in the rabbit. We specifically studied the liver-innervated nitroxidergic neurons that originate in the nodose ganglion (NG), nucleus of the solitary tract (NTS) and dorsal motor vagal nucleus (DMV). Our data showed that BDL resulted in overexpression of NADPH-d/nNOS in the NG, NTS and DMV neurons. Using densitometric analysis, we found a significant increase in NADPH-d expression as a result of BDL in the NG, NTS and DMV (72.6, 79.4 and 57.4% increase, respectively). These findings were corroborated by serum biochemistry and hepatic histopathological examination, which were influenced by NADPH-d/nNOS-generated NO in the liver following BDL. Upregulation of NADPH-d/nNOS expression may have important implications, including (1) facilitation of extrahepatic biliary parasympathetic tone that promotes gallbladder emptying of excess stagnant bile; (2) relaxation of smooth muscles of bile canaliculi thus participating in the pathogenesis of cholestasis; (3) dilation of hepatic sinusoids to counter BDL-induced intrahepatic portal hypertension in which endothelia may be damaged, and (4) alterations in hepatic metabolism, such as glycogenesis, bile formation and secretion, and bilirubin clearance.

Original languageEnglish
Pages (from-to)272-286
Number of pages15
JournalCells Tissues Organs
Volume195
Issue number3
DOIs
Publication statusPublished - Feb 2012
Externally publishedYes

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Keywords

  • Bile duct ligation
  • Dorsal motor vagal nucleus
  • Nicotinamide adenine dinucleotide phosphate-diaphorase
  • Nitric oxide synthase
  • Nodose ganglion
  • Nucleus of solitary tract

ASJC Scopus subject areas

  • Anatomy
  • Histology

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