Deakin University

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Knock out of neuronal nitric oxide synthase exacerbates intestinal ischemia/reperfusion injury in mice

journal contribution
posted on 2012-08-01, 00:00 authored by Leni RiveraLeni Rivera, L Pontell, H-J Cho, P Castelucci, M Thacker, D P Poole, T Frugier, J B Furness
Recent investigation of the intestine following ischemia and reperfusion (I/R) has revealed that nitric oxide synthase (NOS) neurons are more strongly affected than other neuron types. This implies that NO originating from NOS neurons contributes to neuronal damage. However,
there is also evidence of the neuroprotective effects of NO. In this study, we compared the effects of I/R on the intestines of neuronal NOS knockout (nNOS−/−) mice and wildtype mice. I/R caused histological damage to the mucosa and muscle and infiltration of neutrophils into the external muscle layers. Damage to the mucosa and muscle was more
severe and greater infiltration by neutrophils occurred in the first 24 h in nNOS−/− mice. Immunohistochemistry for the contractile protein, α-smooth muscle actin, was used to evaluate muscle damage. Smooth muscle actin occurred in the majority of smooth muscle cells in the external musculature of normal mice but was absent from most cells and
was reduced in the cytoplasm of other cells following I/R. The loss was greater in nNOS−/− mice. Basal contractile activity of the longitudinal muscle and contractile responses to nerve stimulation or a muscarinic agonist were reduced in regions subjected to I/R and the effects were greater in nNOS−/− mice. Reductions in responsiveness also occurred in regions of operated mice not subjected to I/R. This is attributed to post-operative ileus that is not significantly affected by knockout of nNOS. The results indicate that deleterious effects are greater in regions subjected to I/R in mice lacking nNOS compared with normal mice, implying that NO produced by nNOS has protective effects that outweigh any damaging effect of this free radical produced by enteric neurons.



Cell and tissue research






565 - 576




Heidelberg, Germany







Publication classification

C Journal article; C1.1 Refereed article in a scholarly journal

Copyright notice

2012, Springer