Biological Activity
angiotensin-(1–7) (ang-[1–7]) acts as a crucial component of the renin-angiotensin system which can regulate and maintain the blood pressure by offsetting effects of ang ii, a typical vasoconstrictor in vivo. ave 0991, a nonpeptide mimic of ang-(1–7), performs as an agonist of angiotensin-(1-7) receptor. it plays an important role in exploring effects of ang-(1-7) and evaluating the potential of ang-(1-7) as a cardiovascular drug. [1]
in vitro
ave 0991 was found to compete with ang-(1-7) for bovine aortic endothelial cell membrane receptors with an ic50 of 21±35 nm. there was no significant difference in peak concentrations of no and o2- released from ave 0991 treated group and ang-(1-7) treated group. however, the released amount of no was approximately 5 times higher in ave 0991 group than that in ang-(1-7) group. moreover, ave 0091 significantly displaced the binding of i-ang-(1-7) in both mas-transfected monkey kidney cells (cos) and mas-transfected chinese hamster ovary (cho) cells. [1]
in vivo
ave 0091 at a dosage of 0.58 nmol/g resulted in a significant decrease in urinary volume, together with an increase in urinary osmolality in water-loaded c57bl/6 mice. [2] the antidiuretic effect of ave was completely offset by the ang ii antagonists, which indicting a high specificity of ave 0991. since ang ii induced atherogenesis and ang-(1–7) offset ang ii action, it was proved that ave 0991 blocked atherogenesis in apolipoprotein e (apoe)-knockout mice model. [3]
References
[1]wiemer g, dobrucki lw, louka fr, malinski t, heitsch h. ave 0991, a nonpeptide mimic of the effects of angiotensin-(1–7) on the endothelium. hypertension. 2002 dec; 40: 847-52.
[2] pinheiro sv, silva ac, sampaio wo, paula rd, mendes ep, bontempo ed, pesquero jb, walther t, alenina n, bader m, bleich m and santos ra. nonpeptide ave 0991 is an angiotensin-(1-7) receptor mas agonist in the mouse kidney. hypertension. 2004 oct; 44(4):490-6.
[3]toton-zuranska j, gajda m, pyka-fosciak g, kus k, pawlowska m, niepsuj a, wolkow p, olszanecki r, jawien j and korbut r. ave 0991- angiotensin-(1-7) receptor agonist, inhibits atherogenesis in apoe-knockout mice. j physiol pharm. 2010, 61(2):181-183.
