Physiologic studies on nitric oxide in rat small bowel isografts

Area of Science:

• Gastroenterology
• Neuroscience
• Transplantation Biology

Background:

• The enteric nervous system (ENS) regulates intestinal peristalsis, with nonadrenergic noncholinergic (NANC) inhibitory nerves releasing nitric oxide (NO) for relaxation.
• Ischemic and reperfusion injuries during small bowel transplantation (SBT) can damage ENS inhibitory nerves more than excitatory nerves.

Purpose of the Study:

• To evaluate the long-term effects of reperfusion and ischemic injuries on the ENS in transplanted small bowels.
• To assess changes in ENS responses, including NO-mediated effects, in isografted rat jejunum compared to controls.

Main Methods:

• Syngeneic small bowel transplantation (SBT) was performed in Lewis rats.
• Jejunal muscle strips from transplanted and control rats were analyzed using a mechanograph.
• Responses to electrical field stimulation were measured before and after nerve blockade and administration of L-NNA and L-arginine.

Main Results:

• Isografted jejunum showed a dominance of excitatory nerves, especially NANC excitatory nerves, compared to normal jejunum.
• NANC inhibitory nerve function and NO-mediated relaxation were reduced in the isografted jejunum.
• These alterations were observed more than 130 days after SBT.

Conclusions:

• Transplanted small bowels exhibit altered ENS function with increased excitatory and decreased inhibitory nerve activity.
• Reduced NO-mediated NANC inhibitory nerve function likely contributes to long-term dysmotility after SBT.
• ENS injury from ischemia/reperfusion is a significant factor in post-transplant small bowel dysfunction.