An active metabolite of losartan
Ki = 5-20 nM
Losartan Carboxylic Acid, also named E-3174, a physiologically active metabolite of losartan, is a non-peptide, potent angiotensin II (AII) receptor, type 1 (AT1) antagonist, which inhibits the AII induced cellular responses. AII is the primary mediator of the reninangiotensin system, which regulates the blood pressure and body-fluid balance and may be associated with the development of cardiovascular diseases via increasing contractility and cell growth in vascular smooth muscle cells (VSMC).
In vitro: E-3174 potently blocked the specific binding of [125I]-AII to VSMC isolated from rat aorta. E-3174 was able to dampen the platelet-derived growth factor-induced increase in cell DNA synthesis and protein, which led to the blockade of the AII-induced increase in cell protein [1].
In vivo: Rats were administrated E-3174 intravenously at a dose of l.0 mg/kg. After 6 hours, E-3174 markedly attenuated the cardiovascular effects of AII in rats. E-3174 induced a progressive fall in mean arterial pressure and a marked increase in renal flow only [2].
参考文献:
[1].? Li, X. & Widdop, R. Angiotensin Type I Receptor Antagonists CY-11974 and EXP 3174 Cause Selective Renal Vasodilatation in Conscious Spontaneously Hypertensive Rats. Clinical Science, 1996; 91(2): 147-154.
[2].? Sachinidis, A., Ko, Y., Weisser, P., zu BricBkwedde, M., Dsing, R., & Christian, R. et al. EXP3174, a metabolite of losartan (MK954, DuP753) is more potent than losartan in blocking the angiotensin ll-induced responses in vascular smooth muscle cells. Journal of Hypertension. 1993; 11(2): 155-162.
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