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

Rivera, Leni R., Pontell, Louise, Cho, Hyun-Jung, Castelucci, Patricia, Thacker, Michelle, Poole, Daniel P., Frugier, Tony and Furness, John B. 2012, Knock out of neuronal nitric oxide synthase exacerbates intestinal ischemia/reperfusion injury in mice, Cell and tissue research, vol. 349, no. 2, pp. 565-576, doi: 10.1007/s00441-012-1451-3.

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Title Knock out of neuronal nitric oxide synthase exacerbates intestinal ischemia/reperfusion injury in mice
Author(s) Rivera, Leni R.
Pontell, Louise
Cho, Hyun-Jung
Castelucci, Patricia
Thacker, Michelle
Poole, Daniel P.
Frugier, Tony
Furness, John B.
Journal name Cell and tissue research
Volume number 349
Issue number 2
Start page 565
End page 576
Total pages 12
Publisher Springer
Place of publication Heidelberg, Germany
Publication date 2012-08
ISSN 0302-766X
Keyword(s) ischemia
nitric oxide synthase
enteric nervous system
Summary 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 moresevere 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 andwas 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.
Language eng
DOI 10.1007/s00441-012-1451-3
Field of Research 111699 Medical Physiology not elsewhere classified
1116 Medical Physiology
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2012, Springer
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