Enteral feeding reduces endothelial nitric oxide synthase in the caudal intestinal microvasculature of preterm piglets.
The initiation of enteral feeding represents a challenge to the neonatal intestinal microcirculation, especially in preterms where it predisposes to necrotizing enterocolitis (NEC). We hypothesized that a structural microvascular deficiency may occur when enteral feeding is initiated in preterm piglets susceptible to NEC. Stereologic volume densities of a pan-endothelial marker (vWF), and the main vasodilator endothelial nitric oxide synthase (eNOS), were determined along the small intestine of 1) unfed preterm piglets, 2) piglets receiving total parenteral nutrition (TPN) for 2-3 d, and 3) piglets fed 2 d sow's colostrum (TPN+SOW) or milk formula (TPN+FOR) following TPN. In the mucosa, vWF-density decreased in a cranio-caudal direction. A corresponding mucosal eNOS gradient appeared only after initiating enteral feeding. In TPN+SOW, eNOS induction may lag behind the mucosal growth of the caudal region. In TPN+FOR, formula-related factors (i.e. bacteria, cytokines) may suppress mucosal eNOS, indicated by increased stress-sensitive nuclear HIF1alpha staining. The low mucosal endothelial eNOS density was related to the presence of NEC lesions, maybe via increased hypoxia-sensitivity, especially in the caudal region as indicated by nuclear HIF1alpha-staining. Our results suggest an insufficient structural adaptation of the microvasculature to enteral feeding, especially of mucosal eNOS, which may lead to NEC.
van Haver
Els R
ER
Department of Veterinary Medicine, University of Antwerp, 2610 Wilrijk, Belgium.
Oste
Marijke
M
Thymann
Thomas
T
Sys
Stanislas U
SU
Lamers
Wouter H
WH
Weyns
Andre L M
AL
Sangild
Per T
PT
van Ginneken
Christa J
CJ
D000818:Animals; D004730:Endothelium, Vascular / Q000166:cytology; D004750:Enteral Nutrition; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000098:blood supply / Q000201:enzymology*; D008833:Microcirculation; D008954:Models, Biological; D009092:Mucous Membrane / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D012306:Risk; D013552:Swine
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D052250:Nitric Oxide Synthase Type III