Inducible nitric oxide synthase mediates early epithelial repair of porcine ileum.
Reports conflict regarding the effect of nitric oxide (NO) on intestinal epithelium. In chronic injury, NO appears detrimental by combining with reactive oxygen to form potent-free radicals. In contrast, inhibition of NO synthesis after acute injury exacerbates damage and inflammation. Recent studies have disclosed constitutive expression of inducible NO synthase (iNOS) by normal intestinal epithelia, yet little attention has been given to the role of iNOS in acute epithelial repair. We studied the local effects of iNOS on early epithelial repair of porcine ileal mucosa injured by deoxycholate within Ussing chambers. iNOS was constitutively expressed by the villous epithelium, and after deoxycholate injury, iNOS was expressed by injured and detaching enterocytes. Selective inhibition of iNOS abolished increases in NO synthesis and villous reepithelialization after injury. Exogenous L-arginine rescued baseline reepithelialization from NOS inhibitors but was only capable of stimulating additional repair in the presence of serum. These results demonstrate that iNOS-derived NO is a key mediator of early villous reepithelialization following acute mucosal injury.
Gookin
Jody L
JL
Department of Anatomy, Physiological Sciences, and Radiology, School of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA. Jody_Gookin@ncsu.edu
Rhoads
J Marc
JM
Argenzio
Robert A
RA
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D003840:Deoxycholic Acid; D003902:Detergents; D020895:Enterocytes / Q000502:physiology; D005260:Female; D007082:Ileum / Q000201:enzymology / Q000503:physiopathology*; D007410:Intestinal Diseases / Q000139:chemically induced / Q000503:physiopathology*; D007413:Intestinal Mucosa / Q000503:physiopathology*; D008871:Microvilli / Q000201:enzymology / Q000502:physiology; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D013552:Swine; D014945:Wound Healing
D003902:Detergents; D003840:Deoxycholic Acid; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II