Sato M, Murata S, Narita H, Tomita M, Yamashita K, Yamaguchi I
Nihon Yakurigaku Zasshi. 1979 Mar;75(2):99-106. doi: 10.1254/fpj.75.99.
In conscious and anesthetized normotensive rats, intravenous administration of diltiazem (0.1--3 mg/kg) produced a dose-related decrease in blood pressure. Administration of diltiazem (1--50 mg/kg) into the duodenum of anesthetized rats also reduced the blood pressure in a dose related manner. In parallel with the change in blood pressure, the heart rate increased in conscious rats and decreased in anesthetized animals. Such an increase in the heart rate was suppressed by pretreatment with propranolol. Similarly, in conscious spontaneously hypertensive rats (SHR), diltiazem dose-dependently decreased the blood pressure and increased the heart rate after intravenous administration (0.03--1 mg/kg). Oral administration of diltiazem (100 mg/kg) also reduced the blood pressure of SHR. In addition, the progressive increase in blood pressure in young SHR was significantly suppressed by chronic oral administration of diltiazem (30 mg/kg). The blood pressure in conscious renal hypertensive rats was also decreased with diltiazem (50 mg/kg p.o.). On the other hand, it was demonstrated that the pressor responses to norepinephrine and angiotensin II in the anesthetized normotensive rats were non-competitively inhibited by intravenous administration of diltiazem at a dose which had no effect on the blood pressure.
在清醒和麻醉的正常血压大鼠中,静脉注射地尔硫䓬(0.1 - 3毫克/千克)可使血压呈剂量依赖性降低。将地尔硫䓬(1 - 50毫克/千克)注入麻醉大鼠的十二指肠也能以剂量相关的方式降低血压。与血压变化同时,清醒大鼠的心率增加,而麻醉动物的心率降低。这种心率增加被普萘洛尔预处理所抑制。同样,在清醒的自发性高血压大鼠(SHR)中,静脉注射地尔硫䓬(0.03 - 1毫克/千克)后,血压呈剂量依赖性降低,心率增加。口服地尔硫䓬(100毫克/千克)也可降低SHR的血压。此外,慢性口服地尔硫䓬(30毫克/千克)可显著抑制年轻SHR血压的逐渐升高。清醒的肾性高血压大鼠口服地尔硫䓬(50毫克/千克)后血压也降低。另一方面,已证明在麻醉的正常血压大鼠中,静脉注射对地尔硫䓬血压无影响的剂量时,其对去甲肾上腺素和血管紧张素II的升压反应受到非竞争性抑制。