De Wildt D J, Van de Kuil A, Hillen F C, De Groot G
National Institute of Public Health and Environmental Hygiene, Bilthoven, The Netherlands.
Eur J Pharmacol. 1988 Mar 15;147(3):327-34. doi: 10.1016/0014-2999(88)90165-3.
The effect of indapamide on vascular reactivity and its properties as a calcium antagonist were studied in both isolated aorta and perfused renal vasculature of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats. Indapamide was given orally to SHR and WKY rats for 2 weeks at a dose of 5 mg/kg per day. During this period indapamide did not lower blood-pressure in SHR and WKY rats although there was an adequate concentration of indapamide in the blood. There were no differences observed in the vascular reactivity towards noradrenaline and high-K+ in both the above mentioned vessels in either indapamide- or vehicle-pretreated SHR and WKY rats. Verapamil (10(-9)-10(-5) M) caused a concentration-dependent relaxation of high-K+-depolarized aortas and a decrease in the renal-arteriolar perfusion pressure elevated by high-K+ in both strains of rat. However, indapamide (10(-7)-10(-4) M) did not affect the K+-induced effect on either vessel type. Preloading of the vessels in vivo with indapamide for 2 weeks did not influence the results. In conclusion, further evidence has been presented to show that indapamide does not have calcium-antagonist properties in conduit (aorta) or resistance (renal) vessels under hypertensive conditions. Preloading of the vessels with indapamide was not a prerequisite for the demonstration of a pharmacological action of indapamide.
在自发性高血压大鼠（SHR）和正常血压的Wistar Kyoto（WKY）大鼠的离体主动脉和灌注肾血管系统中，研究了吲达帕胺对血管反应性的影响及其作为钙拮抗剂的特性。以每天5mg/kg的剂量给SHR和WKY大鼠口服吲达帕胺，持续2周。在此期间，尽管血液中吲达帕胺浓度充足，但SHR和WKY大鼠的血压并未降低。在吲达帕胺或赋形剂预处理的SHR和WKY大鼠中，上述两种血管对去甲肾上腺素和高钾的血管反应性均未观察到差异。维拉帕米（10⁻⁹ - 10⁻⁵M）可使高钾去极化的主动脉产生浓度依赖性舒张，并使两种品系大鼠中由高钾升高的肾小动脉灌注压降低。然而，吲达帕胺（10⁻⁷ - 10⁻⁴M）对两种血管类型的钾诱导效应均无影响。在体内用吲达帕胺预负荷血管2周并不影响结果。总之，进一步的证据表明，在高血压条件下，吲达帕胺在导管（主动脉）或阻力（肾）血管中不具有钙拮抗剂特性。用吲达帕胺预负荷血管并非证明吲达帕胺药理作用的先决条件。
