Document Detail


Intrathecal neurotensin is hypotensive, sympathoinhibitory and enhances the baroreflex in anaesthetized rat.
MedLine Citation:
PMID:  22035146     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: The neuromodulatory effects of the gut-neuropeptide neurotensin on sympathetic vasomotor tone, central respiratory drive and adaptive reflexes in the spinal cord, are not known.
EXPERIMENTAL APPROACH: Neurotensin (0.5 µM-3 mM) was administered into the intrathecal (i.t.) space at the sixth thoracic spinal cord segment in urethane-anaesthetized, paralysed, vagotomized male Sprague-Dawley rats. Pulsatile arterial pressure, splanchnic sympathetic nerve activity (sSNA), phrenic nerve activity, ECG and end-tidal CO(2) were recorded.
KEY RESULTS: Neurotensin caused a dose-related hypotension, sympathoinhibition and bradycardia. The maximum effects were observed at 3000 µM, where the decreases in mean arterial pressure (MAP), heart rate (HR) and sSNA reached -25 mmHg, -26 beats min(-1) and -26% from baseline, respectively. The sympathetic baroreflex was enhanced. Changes in central respiratory drive were characterized by a fall in the amplitude of the phrenic nerve activity. Finally, administration of SR 142948A (5 mM), a potent, selective antagonist at neurotensin receptors, caused a potent hypotension (-35 mmHg), bradycardia (-54 beats min(-1) ) and sympathoinhibition (-44%). A reduction in the amplitude and frequency of the phrenic nerve activity was also observed.
CONCLUSIONS AND IMPLICATIONS: The data demonstrate that neurotensin plays an important role in the regulation of spinal cardiovascular function, affecting both tone and adaptive reflexes.
Authors:
B Zogovic; P M Pilowsky
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  166     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-11     Completed Date:  2012-08-06     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  378-89     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.
Affiliation:
Australian School of Advanced Medicine, Macquarie University, Sydney, NSW, Australia.
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MeSH Terms
Descriptor/Qualifier:
Animals
Baroreflex / drug effects*
Blood Pressure / drug effects*
Bradycardia / chemically induced
Carbon Dioxide / metabolism
Dose-Response Relationship, Drug
Electrocardiography
Heart Rate / drug effects*
Hypotension / chemically induced
Injections, Spinal
Male
Neurotensin / administration & dosage,  metabolism,  pharmacology*
Phrenic Nerve / metabolism
Rats
Rats, Sprague-Dawley
Spinal Cord / drug effects,  metabolism
Splanchnic Nerves / metabolism
Chemical
Reg. No./Substance:
124-38-9/Carbon Dioxide; 39379-15-2/Neurotensin
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