LACK OF NEURONAL NITRIC-OXIDE SYNTHASE IN NERVE-FIBERS OF AGANGLIONICINTESTINE - A CLUE TO HIRSCHSPRUNGS-DISEASE

The lack of nonadrenergic, noncholinergic (NANC) inhibitory innervatio n in aganglionic intestine is typical of Hirschsprung's disease. Sever al neuropeptides participating in the intestinal NANC innervation are greatly reduced in aganglionic intestine. However, these findings do n ot fully explain the pathophysiology of the disease. Recently, nitric oxide (NO) has been presented as a potent smooth muscle relaxant, and the enzyme responsible for its formation, nitric oxide synthase (NOS) has been demonstrated in neuronal elements in both the central and per ipheral nervous system, In our study, nicotinamide adenine dinucleotid e phosphate (NADPH)-diaphorase staining, a marker for NOS, and NOS imm unohistochemistry revealed a dense innervation of the smooth muscle la yers and the myenteric ganglia in ganglionic non afflicted intestine f rom patients with Hirschsprung's disease. By contrast, there was an al most complete lack of NOS-immunoreactive and NADPH-diaphorase-positive nerve fibers in the afflicted aganglionic bowel. NOS and vasoactive i ntestinal peptide were found to be partially colocalized in nerve fibe rs and neuronal cell bodies in the ganglionic but not in the aganglion ic intestine. The lack of NO-producing nerve fibers in the aganglionic intestine probably contributes to the inability of the smooth muscle to relax, thereby causing lack of peristalsis in Hirschsprung's diseas e.