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[Nitric oxide and Hirschsprung's disease: a causal relation biochemically, immunohistochemically and functionally
J M Gil-Vernet1, C Marhuenda, J Boix-Ochoa
1Departamento de Cirugía Pediátrica, Hospital Universitario Materno-Infantil Vall d'Hebrón, Barcelona.
Summary
Hirschsprung's disease may involve absent nitric oxide synthetase (NOS) in aganglionic colon segments. This study found NOS activity and specific staining absent in affected areas, correlating with impaired muscle function.
Area of Science:
- Gastroenterology
- Neurogastroenterology
- Molecular Biology
Background:
- Hirschsprung's disease is characterized by absent enteric ganglia in the distal colon.
- Impaired nonadrenergic-noncholinergic inhibitory neurotransmission is implicated in Hirschsprung's disease.
- Nitric oxide (NO) is a potential neurotransmitter involved in intestinal motility.
Purpose of the Study:
- To investigate the activity and localization of nitric oxide synthetase (NO-S) in ganglionic and aganglionic colon segments.
- To assess the in vitro motor activity of muscle strips from these segments.
- To evaluate the response of muscle strips to NO donors and antagonists.
Main Methods:
- Quantification of NO synthetase activity via 14C-L-arginine to 14C-L-citrulline conversion in tissue homogenates.
- Immunohistochemical staining using an antibody against NO synthetase.
- In vitro measurement of muscle strip contractility and response to sodium nitroprusside (NO donor) and L-NAME (NO antagonist).
Main Results:
- NO synthetase activity was undetectable in aganglionic segments but present in ganglionic segments.
- Immunohistochemistry revealed NO-S absence in the myenteric plexus of aganglionic segments and presence in ganglionic segments.
- Aganglionic segments lacked summation contractions, while both segments relaxed significantly with sodium nitroprusside.
Conclusions:
- The absence of NO synthetase in the aganglionic colon suggests a deficiency in nitric oxide production.
- This NO deficiency may contribute to the impaired inhibitory neurotransmission observed in Hirschsprung's disease.
- Further research into NO's role could offer new therapeutic targets for Hirschsprung's disease.