Oral Delivery of L‐arginine Stimulates Prostaglandin‐dependent Secretory Diarrhea in Cryptosporidium parvum–infected Neonatal Piglets

Abstract

Objectives: To determine if oral supplementation with L-arginine could augment nitric oxide (NO) synthesis and promote epithelial defense in neonatal piglets infected with Cryptosporidium parvum. Materials and Methods: Neonatal piglets were fed a liquid milk replacer and on day 3 of age infected or not with 10⁸C parvum oocysts and the milk replacer supplemented with L-arginine or L-alanine. Milk consumption, body weight, fecal consistency, and oocyst excretion were recorded daily. On day 3 postinfection, piglets were euthanized and serum concentration of NO metabolites and histological severity of villous atrophy and epithelial infection were quantified. Sheets of ileal mucosa were mounted in Ussing chambers for measurement of barrier function (transepithelial resistance and permeability) and short-circuit current (an indirect measurement of Cl⁻ secretion in this tissue). Results: C parvum–infected piglets had large numbers of epithelial parasites, villous atrophy, decreased barrier function, severe watery diarrhea, and failure to gain weight. L-Arginine promoted synthesis of NO by infected piglets, which was unaccompanied by improvement in severity of infection but rather promoted epithelial chloride secretion and diarrhea. Epithelial secretion by infected mucosa from L-arginine-supplemented piglets was fully inhibited by the cyclooxygenase inhibitor indomethacin, indicating that prostaglandin synthesis was responsible for this effect. Conclusions: Results of these studies demonstrate that provision of additional NO substrate in the form of L-arginine incites prostaglandin-dependent secretory diarrhea and does not promote epithelial defense or barrier function of C parvum–infected neonatal ileum.