Soluble β-amyloid (Aβ) 40 causes attenuation or potentiation of noradrenaline-induced vasoconstriction in rats depending upon the concentration employed

Soluble p-amyloid (Abeta) 40 peptide (1muM) has been reported to enhance phenylephrine and endothelin-I 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 muM Abeta 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(5)) values obtained for aortic rings from WKY and SHR, however, exhibited no changes. Contrasting with the effects observed with 1 mum Abeta 40, treatment of SD aortic rings with 5 muM Abeta 40 resulted in potentiation of NA-induced constriction and a 46% decrease in EC50 values. We hypothesise that at low concentrations Abeta 40 may cause attenuation of NA-induced constriction by dint of enhanced endothelial vasodilator (nitric oxide, prostacyclin) synthesis. By contrast, at higher concentrations Abeta 40 may potentiate vasoconstriction via the generation of toxic Abeta oligomers which act on the endothelium to reduce vasodilator output. (C) 2004 Elsevier Ireland Ltd. All rights reserved.