Endothelial nitric oxide synthase in human intestine resected for necrotizing enterocolitis.
OBJECTIVE
To determine the expression and function of endothelial nitric oxide synthase (eNOS) in submucosal arterioles harvested from human intestine resected for necrotizing enterocolitis (NEC) or congenital bowel disease.


METHODS
eNOS expression was determined by using immunohistochemistry. The arteriolar diameter was measured in vitro at pressures of 10 to 40 mm Hg and also in response to the eNOS agonist acetylcholine (ACh), the exogenous nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine, and the smooth muscle relaxant papaverine. Arteriolar release of NO in response to ACh was determined with a Sievers NOAnalyzer. Hemodynamics were also determined at flow rates of 50 and 100 microL/min.


RESULTS
eNOS was present in microvessels from both groups, but NEC arterioles failed to demonstrate physiological evidence of eNOS function: they constricted in response to pressure, failed to dilate or generate NO in response to ACh, and failed to dilate in response to flow. However, they dilated in response to exogenous NO and papaverine, indicating functional vascular smooth muscle and vasodilator reserve.


CONCLUSIONS
eNOS-derived NO, a vasodilator in the newborn intestine, did not contribute to vasoregulation in arterioles harvested from intestine resected for NEC. These vessels were constricted; lack of eNOS-derived NO may contribute to this vasoconstriction.
Nowicki
Philip T
PT
Department of Pediatrics, Department of Surgery, The Ohio State University, Columbus, Ohio, USA. nowickip@pediatrics.ohio-state.edu <nowickip@pediatrics.ohio-state.edu>
Caniano
Donna A
DA
Hammond
Sue
S
Giannone
Peter J
PJ
Besner
Gail E
GE
Reber
Kristina M
KM
Nankervis
Craig A
CA
D001160:Arterioles / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D001783:Blood Flow Velocity; D020345:Enterocolitis, Necrotizing / Q000201:enzymology* / Q000503:physiopathology / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D007421:Intestine, Small / Q000098:blood supply / Q000201:enzymology* / Q000601:surgery; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D012720:Severity of Illness Index; D014664:Vasodilation
D015415:Biomarkers; D052250:Nitric Oxide Synthase Type III