体外研究
The specific binding of [125I]-angiotensin II to VSMC is inhibited by Losartan Carboxylic Acid (E-3174) with an IC
50
of 1.1 nM. Losartan Carboxylic Acid abolishes the angiotensin II-induced formation of inositolphosphates in VSMC. Losartan Carboxylic Acid inhibits the angiotensin II-induced elevation of intracellular cytosolic Ca2+ concentration with an IC
50
of 5 nM. Losartan Carboxylic Acid is more effective than losartan in blocking the angiotensin II-induced increase in Egr-1 mRNA. Losartan Carboxylic Acid inhibits the angiotensin II-induced cell protein synthesis with an IC
50
of 3 nM.
体内研究
Losartan Carboxylic Acid (E-3174) (0.1 mg/kg; i.v. followed by 0.02 mg/kg/h for 5.5 h) induces a similar level of inhibition (87±4%) of the pressor responses to angiotensin I.
Intravenous Losartan Carboxylic Acid (0.1 mg/kg+0.01 mg/kg/min) is infused in anesthetized dogs with recent (8.1±0.4 days) anterior myocardial infarction. Electrolytic injury of the left circumflex coronary artery to induce thrombotic occlusion and posterolateral ischemia is initiated 1 h after the start of treatment.
Animal Model:
Mongrel dogs of either sex, weighing 15-25 kg
Dosage:
0.1 mg/kg (followed by 0.02 mg/kg/h)
Administration:
i.v. for 5.5 hours
Result:
The pressor response was reduced by 87±4%.
