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.
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
Christopher C T
CC
Smith
Lee
L
Stanyer
D John
DJ
Betteridge
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