Calcimimetic, AMG 073, induces relaxation on isolated rat aorta.

Calcimimetics are a class of compounds that positively modulate the calcium-sensing receptor (CaR) by allosterically increasing the affinity of the receptor for extracellular Ca(2+). In this study we have investigated the effects of the clinically used calcimimetic, AMG 073, on contractility of the rat aorta by wire myography. AMG 073 elicited a concentration-dependent vasodilatation of the precontracted aorta. Inhibition of endothelium function by L-NAME and indomethacin reduced AMG 073-induced relaxation of the vessel precontracted with phenylephrine, but not with 125 mM K(+). The vasodilatory effect could be mediated by the CaR or/and a direct action on the ion channels. Intriguingly, CaR agonists, neomycin and gadolinium, did not have any effect on the contractility of the aorta. Immunohistochemical staining of the aorta with two CaR specific antibodies demonstrated the presence of the CaR protein, predominantly in endothelial and adventitial layers.