生物活性

• 描述Angiotensin-(1–7) (Ang-[1–7]), a biologically active component of the renin-angiotensin system, regulates blood pressure by counteracting the vasoconstrictor and proliferative effects of Ang II. AVE 0991 is a novel nonpeptide compound that evoked effects similar to Ang-(1–7) on the endothelium. AVE 0991 competed for high-affinity binding of [¹²⁵I]-Ang-(1–7) to bovine aortic endothelial cell membranes with IC₅₀ values of 21 ± 35 nM (n=3). The released amount of bioactive NO was ≈5 times higher for AVE 0991 (10 μmol/L) in comparison to Ang-(1–7) (10 μmol/L). In water-loaded C57BL/6 mice, AVE 0991 (0.58 nmol/g body weight) produced a significant reduction in urinary volume (0.06+/-0.03 mL/60 min [n=9] versus 0.27+/-0.05 [n=9]; P<0.01), associated with an increase in urinary osmolality. In infarcted male Wistar rats, AVE-0991 significantly attenuated the decrease in systolic tension (sham operated, 13.00 ± 1.02 g; infarction, 7.18 ± 0.66 g; AVE treated, 9.23 ± 1.05 g, n = 5), +dT/dt, -dT/dt, and heart rate induced by myocardial infarction. Furthermore, AVE-0991 significantly decreased the infarcted area (6.98 ± 1.01 vs. 3.94 ± 1.04 mm² in AVE-treated rats).

• 动物研究
  剂量	Mice: 9.0 mg/kg[3] (s.c.) Rat: 0.5 mg/kg[4] (osmotic minipump); 20 mg/kg[5] (p.o.); 576 μg/kg/day[6] (i.p.)
  给药途径	s.c., p.o., i.p.