生物活性

• 描述Angiotensin receptor blockade and neprilysin (NEP) inhibition together offer potential benefits for the treatment of hypertension and heart failure. LCZ696, composed of valsartan and sacubitril with a molar ratio of 1:1, is an oral bioactive, dual-acting angiotensin receptor-neprilysin inhibitor (ARNi) for the treatment of hypertension and heart failure. H9C2 cells were pretreated with LCZ696 at concentrations of 1, 10, or 30 μM for 30 min and then stimulated with high glucose (HG) for 48 h. HG- or diabetes-induced JNK/p38MAPK phosphorylation and NF-kB nuclear translocation were inhibited by the administration of LCZ696. Oral administration of LCZ696 caused dose-dependent increases in atrial natriuretic peptide immunoreactivity (due to NEP inhibition) in Sprague-Dawley rats and provided sustained, dose-dependent blood pressure reductions in hypertensive double-transgenic rats. Adult male Sprague–Dawley rats were randomized to treatment for 4 weeks with LCZ696 (68 mg/kg body weight perorally; myocardial infarction (MI) -ARNi, n=11), and the degree of fibrosis both in noninfarcted remote myocardium and in the peri-infarct zone was significantly reduced.

• 动物研究
  剂量	Mice: 60 mg/kg[3] (p.o.), 6 mg/kg[4] (p.o.) Rat: 2 mg/kg - 60 mg/kg[5] (p.o.) Beagle dog: 15 mg/kg, 45 mg/kg[6] (p.o.)
  给药途径	p.o.