Morishita S, Nishimura K, Kato E, Shirahase H, Osumi S, Kitao K, Seki T
Nihon Yakurigaku Zasshi. 1982 Mar;79(3):137-46.
Antihypertensive and diuretic actions of indapamide (SE-1520) were investigated in rats and compared with those of trichlormethiazide (TCMT). In normotensive rats, indapamide in a dose of 100 mg/kg p.o. did not show a significant effect on the blood pressure. In DOCA-saline and uni-nephrectomized DOCA-saline hypertensive rats, indapamide above 1 mg/kg and TCMT above 3 mg/kg with single oral or repetitive administration for 2 weeks reduced the blood pressure level. In spontaneously hypertensive rats (SHR), both indapamide and TCMT lowered the blood pressure with single doses above 10 mg/kg or repetitive doses above 3 and 10 mg/kg, respectively. In the diuretic test using normal rats, indapamide in doses ranging from 0.1 to 30 mg/kg increased urine volume and urinary electrolyte excretion. TCMT showed a more potent diuretic action at a lower dose level. In SHR, indapamide and TCMT produced a greater urine volume and electrolytes excretion. Indapamide inhibited the carbonic anhydrase activity and the potency was about 1/25 of that of acetazolamide in vitro. The antihypertensive activity of indapamide was more potent than that of TCMT and the reverse order to that of their diuretic potencies. It is suggested that the mechanism of antihypertensive effect of indapamide is different from that of TCMT.
研究了吲达帕胺（SE - 1520）在大鼠体内的降压和利尿作用，并与三氯噻嗪（TCMT）进行了比较。在正常血压大鼠中，口服剂量为100 mg/kg的吲达帕胺对血压无显著影响。在去氧皮质酮盐（DOCA） - 盐和单侧肾切除的DOCA - 盐高血压大鼠中，单次口服或重复给药2周，剂量高于1 mg/kg的吲达帕胺和高于3 mg/kg的TCMT可降低血压水平。在自发性高血压大鼠（SHR）中，吲达帕胺和TCMT分别单次给药剂量高于10 mg/kg或重复给药剂量高于3和10 mg/kg时均可降低血压。在正常大鼠的利尿试验中，剂量范围为0.1至30 mg/kg的吲达帕胺可增加尿量和尿电解质排泄。TCMT在较低剂量水平时利尿作用更强。在SHR中，吲达帕胺和TCMT产生的尿量和电解质排泄量更大。吲达帕胺在体外抑制碳酸酐酶活性，其效力约为乙酰唑胺的1/25。吲达帕胺的降压活性比TCMT更强，且与其利尿效力的顺序相反。提示吲达帕胺的降压作用机制与TCMT不同。
