J Physiol Society Meetings
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Physiol Volume 581, Number 3, 1293-1307, June 15, 2007 DOI: 10.1113/jphysiol.2007.130872
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
581/3/1293    most recent
jphysiol.2007.130872v1
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chan, J. Y. H.
Right arrow Articles by Chang, A. Y. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chan, J. Y. H.
Right arrow Articles by Chang, A. Y. W.
Related Collections
Right arrow Integrative

INTEGRATIVE

Transcriptional up-regulation of nitric oxide synthase II by nuclear factor-{kappa}B at rostral ventrolateral medulla in a rat mevinphos intoxication model of brain stem death

 Julie Y. H. Chan1, Carol H. Y. Wu2, Ching-Yi Tsai2, Hsiao-Lei Cheng2, Kuang-Yu Dai2, Samuel H. H. Chan2 and Alice Y. W. Chang2

1 Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, Republic of China
2 Center for Neuroscience, National Sun Yat-sen University, Kaohsiung, Taiwan, Republic of China

As the origin of a ‘life-and-death’ signal that reflects central cardiovascular regulatory failure during brain stem death, the rostral ventrolateral medulla (RVLM) is a suitable neural substrate for mechanistic delineation of this vital phenomenon. Using a clinically relevant animal model that employed the organophosphate pesticide mevinphos (Mev) as the experimental insult, we evaluated the hypothesis that transcriptional up-regulation of nitric oxide synthase I or II (NOS I or II) gene expression by nuclear factor-{kappa}B (NF-{kappa}B) on activation of muscarinic receptors in the RVLM underlies brain stem death. In Sprague-Dawley rats maintained under propofol anaesthesia, co-microinjection of muscarinic M2R (methoctramine) or M4R (tropicamide), but not M1R (pirenzepine) or M3R (4-diphenylacetoxy-N-dimethylpiperidinium) antagonist significantly reduced the enhanced NOS I–protein kinase G signalling (‘pro-life’ phase) or augmented NOS II–peroxynitrite cascade (‘pro-death’ phase) in ventrolateral medulla, blunted the biphasic increase and decrease in baroreceptor reflex-mediated sympathetic vasomotor tone that reflect the transition from life to death, and diminished the elevated DNA binding activity or nucleus-bound translocation of NF-{kappa}B in RVLM neurons induced by microinjection of Mev into the bilateral RVLM. However, NF-{kappa}B inhibitors (diethyldithiocarbamate or pyrrolidine dithiocarbamate) or double-stranded {kappa}B decoy DNA preferentially antagonized the augmented NOS II–peroxynitrite cascade and the associated cardiovascular depression exhibited during the ‘pro-death’ phase. We conclude that transcriptional up-regulation of NOS II gene expression by activation of NF-{kappa}B on selective stimulation of muscarinic M2 or M4 subtype receptors in the RVLM underlies the elicited cardiovascular depression during the ‘pro-death’ phase in our Mev intoxication model of brain stem death.

(Received 21 February 2007; accepted after revision 20 March 2007; first published online 29 March 2007)
Corresponding author A. Y. W. Chang: Center for Neuroscience, National Sun Yat-sen University, Kaohsiung 80424, Taiwan, Republic of China. Email: achang{at}mail.nsysu.edu.tw






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2007 The Physiological Society.