Overview
- Mederski, W.W. et al. (1994) J. Med. Chem. 37, 1632.
Alomone Labs EMD 66684 inhibits the activation of AT1R expressed in CHO-K1-mt aequorin-Gα16 cells.Dose-response curve for the inhibition of AT1R expressed in CHO-K1-mt aequorin-Gα16 cells. Ca2+ response, as detected by the increase in aequorin derived fluorescence following 0.04 nM Angiotensin II application, was inhibited by increasing concentrations of EMD 66684 (#E-160). 10 nM EMD 66684 fully inhibited the activation by Angiotensin II.
Angiotensin II is responsible for vasoconstriction in the renin-angiotensin system. In addition to its direct effect on blood vessels it stimulates the synthesis and release of aldosterone and also promotes renal tubular reabsorption of sodium, resulting in water retention1.
EMD 66684 is a synthetic antagonist of the Angiotensin II type 1 receptor. It has an effective concentration of 1-100 nM. EMD 66684 completely attenuates Ang II-induced increases in basal and nerve stimulated neuropeptide Y (NPY) overflow from mesenteric arterial beds in a model of spontaneously hypertensive rats. In the same model EMD 66684 also attenuated the effect of Ang II on perfusion pressure2.
The antagonistic properties of EMD are also demonstrated in an experiment examining the relation between lipid rafts and angiotensin II receptors. EMD reduces Ang II-induced proliferation of neonatal pig glomerular mesangial cells. EMD also inhibits Ang II-mediated Ca2+ currents and the signal pathway initiated by calcium/calmodulin dependent protein kinases (CAMK) in the same cells3.
