Soluble beta-amyloid (A beta) 40 causes attenuation or potentiation of noradrenaline-induced vasoconstriction in rats depending upon the concentration employed.
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.
Smith
Christopher C T
CC
Department of Medicine, Royal Free and University College Medical School, Sir Jules Thorn Institute, The Middlesex Hospital, Mortimer Street, London W1N 8AA, UK. christopher.smith@ucl.as.uk
Stanyer
Lee
L
Betteridge
D John
DJ
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001011:Aorta; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D009638:Norepinephrine / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D014661:Vasoconstriction / Q000187:drug effects*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D009638:Norepinephrine