Document Detail

Soluble beta-amyloid (A beta) 40 causes attenuation or potentiation of noradrenaline-induced vasoconstriction in rats depending upon the concentration employed.
MedLine Citation:
PMID:  15308313     Owner:  NLM     Status:  MEDLINE    
Soluble beta-amyloid (A beta) 40 peptide (1 microM) has been reported to enhance phenylephrine and endothelin-1 induced contraction of rat aortic rings. We conducted similar experiments with aortic rings from Sprague-Dawley (SD), Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats but employing noradrenaline (NA) as the vasoconstrictor. Unlike previous studies we found that, rather than enhancing agonist-induced contraction, 1 microM A beta 40 attenuated the vasoconstrictive responses to NA. With aortic rings from SD rats the attenuation of contractile responses was coupled with a 99% increase in NA EC(50) values. EC(50) values obtained for aortic rings from WKY and SHR, however, exhibited no changes. Contrasting with the effects observed with 1 microM A beta 40, treatment of SD aortic rings with 5 microM A beta 40 resulted in potentiation of NA-induced constriction and a 46% decrease in EC(50) values. We hypothesise that at low concentrations A beta 40 may cause attenuation of NA-induced constriction by dint of enhanced endothelial vasodilator (nitric oxide, prostacyclin) synthesis. By contrast, at higher concentrations A beta 40 may potentiate vasoconstriction via the generation of toxic A beta oligomers which act on the endothelium to reduce vasodilator output.
Christopher C T Smith; Lee Stanyer; D John Betteridge
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neuroscience letters     Volume:  367     ISSN:  0304-3940     ISO Abbreviation:  Neurosci. Lett.     Publication Date:  2004 Aug 
Date Detail:
Created Date:  2004-08-13     Completed Date:  2004-11-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7600130     Medline TA:  Neurosci Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  129-32     Citation Subset:  IM    
Department of Medicine, Royal Free and University College Medical School, Sir Jules Thorn Institute, The Middlesex Hospital, Mortimer Street, London W1N 8AA, UK.
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MeSH Terms
Amyloid beta-Protein / pharmacology*
Dose-Response Relationship, Drug
Drug Interactions
Norepinephrine / pharmacology*
Peptide Fragments / pharmacology*
Rats, Inbred SHR
Rats, Inbred WKY
Rats, Sprague-Dawley
Species Specificity
Vasoconstriction / drug effects*
Reg. No./Substance:
0/Amyloid beta-Protein; 0/Peptide Fragments; 0/amyloid beta-protein (1-40); 51-41-2/Norepinephrine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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