Oral delivery of L-arginine stimulates prostaglandin-dependent secretory diarrhea in Cryptosporidium parvum-infected neonatal piglets.
OBJECTIVE
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.


METHODS
Neonatal piglets were fed a liquid milk replacer and on day 3 of age infected or not with 10(8) C. 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.
Gookin
Jody L
JL
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh 27606, USA. jody_gookin@ncsu.edu
Foster
Derek M
DM
Coccaro
Maria R
MR
Stauffer
Stephen H
SH
D000409:Alanine / Q000008:administration & dosage; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001120:Arginine / Q000008:administration & dosage*; D001284:Atrophy; D002712:Chlorides / Q000378:metabolism; D003457:Cryptosporidiosis / Q000469:parasitology / Q000503:physiopathology / Q000628:therapy*; D016785:Cryptosporidium parvum / Q000254:growth & development*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003967:Diarrhea / Q000469:parasitology / Q000503:physiopathology / Q000628:therapy*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004750:Enteral Nutrition; D007082:Ileum / Q000469:parasitology / Q000473:pathology / Q000502:physiology; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000469:parasitology / Q000473:pathology; D009569:Nitric Oxide / Q000096:biosynthesis*; D033661:Oocysts / Q000254:growth & development; D010270:Parasite Egg Count; D011453:Prostaglandins / Q000096:biosynthesis*; D011897:Random Allocation; D012720:Severity of Illness Index; D013552:Swine
D002712:Chlorides; D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D009569:Nitric Oxide; D001120:Arginine; D000409:Alanine; D007213:Indomethacin