Neuronal nitric oxide synthase immunoreactivity in the guinea-pig liver: distribution and colocalization with neuropeptide Y and calcitonin gene-related peptide

Liver. 2001 Dec;21(6):374-9. doi: 10.1034/j.1600-0676.2001.210602.x.


Aims/background: The innervation pattern of the guinea-pig liver is similar to that of the human liver. However, many aspects of the distribution of the neuronal isoform of the enzyme nitric oxide synthase (nNOS) in the guinea-pig liver and its colocalization with neuropeptides remain to be elucidated.

Methods: The distribution of nNOS was studied in fixed guinea-pig liver by light microscopic immunohistochemistry. Confocal analysis was used to determine its colocalization with neuropeptide Y (NPY) or calcitonin gene-related peptide (CGRP).

Results: nNOS-immunoreactive (nNOS-IR) nerves were observed in relation to hilar and interlobar vessels and in Glisson's capsule. A few nNOS-IR ganglia were observed in the extrahepatic bile duct and close to the interlobar portal triads. In addition, nNOS-IR fibers were located in the interlobular portal triads and pervading the parenchyma. Moreover, nNOS-IR nerves were demonstrated for the first time in the larger central veins and in the hepatic vein. nNOS-NPY and nNOS-CGRP colocalizations were detected in the fibromuscular layer of the bile duct and periductal plexus, respectively.

Conclusions: These results support the phylogenetic conservation of the nNOS-IR hepatic innervation and its possible contribution to the regulation of hepatic blood flow and certain hepatic functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcitonin Gene-Related Peptide / metabolism*
  • Fluorescent Antibody Technique, Indirect
  • Guinea Pigs
  • Liver / innervation*
  • Male
  • Microscopy, Confocal
  • Neuropeptide Y / metabolism*
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type I
  • Peripheral Nervous System / enzymology*


  • Neuropeptide Y
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type I
  • Calcitonin Gene-Related Peptide