P0146 PP PLASMA NITRITE AND MUSCULAR NEURAL NITRIC OXIDE SYNTHASE IN INFANTILE HYPERTROPHIC PYLORIC STENOSIS

Abstract

Introduction: Nitric oxide (NO) is well known to participate in the regulation of smooth muscle contractility. We sought to investigate whether plasma NO and pylorus NO synthases (NOS) expression are involved in infantile hypertrophic pyloric stenosis (IHPS). Methods: Blood and pylorous biopsies from thirteen IHPS patients were studied and compared to age-matched normal infants. Plasma nitrite (NO2-) and nitrate (NO3-) levels were detected by an NO analyzer. Pylorus biopsies were collected for immunohistochemical identification of NOS isoform expression in nerve cells, fibers and endothelium in the pyloric muscles. Results: Plasma nitrite levels in the 13 IHPS patients were lower than in the age-matched control group (0.97+/− 0.19uM vs. 3.39 +/− 0.80uM, p<0.001), although the plasma nitrate levels were no different between the two groups (47.75 +/−17.02uM vs. 47.33+/− 27.57uM, p=0.96). Patients with IHPS were determined to have muscular hypertrophy of the circular muscle of the pylorus on pathological examination. Moreover, it was found that in the nerve fibers of the pylorus circular muscle biopsies from 13 IHPS patients there was an absence of neuronal NOS (nNOS) expression as determined by immunostaining. In contrast, nNOS immunostaining was detectable in the pylorus circular muscle biopsies from 9 normal controls. The decreased plasma nitrite levels returned to normal (3.27 +/− 0.77uM) after surgical pyloromyotomy. Conclusion: Lower nNOS expression, combined with decreased plasma nitrite, may be responsible for pylorospasm in infantile hypertrophic pyloric stenosis. The lower nitrite levels in IHPS patients recovered after surgical myotomy of the pylorus, suggesting that pharmacological modulation of nNOS expression or NO production in the gut may serve as an alternative treatment for infants without surgery.