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Nitric oxide synthase activity in infantile hypertrophic pyloric stenosis
J M Vanderwinden1, P Mailleux, S N Schiffmann
1Laboratory of Neuropathology and Neuropeptide Research, Erasme Academic Hospital, Brussels, Belgium.
Insights
A defect in nitric oxide production may cause infantile hypertrophic pyloric stenosis (IHPS). Researchers found a lack of nitric oxide synthase in pyloric tissue from IHPS patients, suggesting a link to pylorospasm.
Area of Science:
- Gastroenterology
- Pediatric Surgery
- Neurogastroenterology
Background:
- Infantile hypertrophic pyloric stenosis (IHPS) causes gastric-outlet obstruction due to enlarged pyloric musculature.
- The exact cause of IHPS is unknown, but impaired pyloric relaxation (pylorospasm) is suspected.
- Nitric oxide (NO) mediates digestive tract relaxation, suggesting a potential role for NO deficiency in pylorospasm.
Purpose of the Study:
- To investigate the role of nitric oxide synthase (NOS) in the pyloric tissue of infants with IHPS.
- To determine if a deficiency in NOS activity contributes to the pylorospasm observed in IHPS.
Main Methods:
- Pyloric tissue samples were obtained from nine infants with IHPS and seven controls.
- NADPH diaphorase histochemical staining was used to detect NOS activity.
- Immunohistochemistry with a tau antiserum identified the enteric nervous system.
Main Results:
- NADPH diaphorase activity was localized to the enteric nervous system and blood vessels in control tissues.
- In IHPS patients, enteric nerve fibers in the hypertrophied circular muscle lacked diaphorase activity.
- Diaphorase activity was preserved in the myenteric plexus and longitudinal muscle of IHPS patients.
Conclusions:
- A deficiency in nitric oxide synthase in pyloric nerve fibers is implicated in pylorospasm in IHPS.
- This finding suggests a specific molecular mechanism underlying IHPS pathophysiology.
- Targeting NO pathways may offer therapeutic potential for IHPS.
Background:
Hypertrophic pyloric stenosis is a common infantile disorder characterized by enlarged pyloric musculature and gastric-outlet obstruction. Its physiopathologic mechanism is not known, but a defect in pyloric relaxation (pylorospasm) has been postulated. Nitric oxide is a mediator of relaxation in the mammalian digestive tract, raising the possibility that pylorospasm could be caused by a defect in nitric oxide production. Since neuronal nitric oxide synthase and NADPH diaphorase are identical, we used the NADPH diaphorase histochemical reaction to study the distribution of nitric oxide synthase in pyloric tissue from patients with infantile hypertrophic pyloric stenosis.
Methods:
We studied pyloric tissue from nine infants with infantile hypertrophic pyloric stenosis and seven control infants and children. Cryostat sections were processed for NADPH diaphorase histochemical analysis. A polyclonal tau antiserum was used to identify the enteric nervous system by immunohistochemical methods.
Results:
NADPH diaphorase activity was restricted to the enteric nervous system and blood vessels. In the pyloric tissues from the control patients, intense diaphorase activity was present in the nerve fibers of the circular musculature, in the neurons and nerve bundles of the myenteric plexus, and in some nerve fibers of the longitudinal musculature. In the pyloric tissues from patients with infantile hypertrophic pyloric stenosis, the enteric nerve fibers in the hypertrophied circular musculature were enlarged and distorted and did not contain diaphorase activity, whereas the activity in the myenteric plexus and the longitudinal musculature was preserved.
Conclusions:
We suggest that a lack of nitric oxide synthase in pyloric tissue is responsible for pylorospasm in infantile hypertrophic pyloric stenosis.