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急性和慢性西拉普利治疗对自发性高血压大鼠的影响。

Effects of acute and chronic cilazapril treatment in spontaneously hypertensive rats.

作者信息

Fischli W, Hefti F, Clozel J P

机构信息

Pharmaceutical Research Department, F. Hoffmann-La Roche & Co. Ltd, Basle, Switzerland.

出版信息

Br J Clin Pharmacol. 1989;27 Suppl 2(Suppl 2):151S-158S. doi: 10.1111/j.1365-2125.1989.tb03476.x.

Abstract
  1. The effects of acute and chronic treatment with cilazapril, a new ACE inhibitor, on peripheral vasculature and renal excretory function were assessed in spontaneously hypertensive rats. Regional blood flow and cardiac output were measured by the radioactive microspheres technique. 2. Acute treatment (3 mg kg-1 intravenously) reduced mean arterial blood pressure from 171 +/- 7 to 140 241 +/- 7 mm Hg (P less than 0.001), chronic treatment (1 x 10 mg kg-1 day-1 orally for 9 weeks) from 191 +/- 5 to 122 +/- 3 mm Hg P less than 0.001). With both kinds of treatments cardiac output was unchanged. Heart rate was slightly decreased (-9%, P less than 0.05) with chronic treatment. Acutely, the main effect of cilazapril was a decrease of the renal vascular resistance (-41%, P less than 0.001) associated with an increase of the fraction of the cardiac output distributed to the kidney (+46%, P less than 0.001). Chronically, cilazapril decreased regional vascular resistance in most of the peripheral vascular beds except the heart. 3. With a high dose of cilazapril (10 mg kg-1 orally) both acute and chronic treatment increased diuresis (+107% and +92%, P less than 0.001) and natriuresis (/124% and +111%, P less than 0.001) with a slight increase in kaliuresis. However, with a low dose (1 mg kg-1 orally) the kidneys responded only to chronic treatment. 4. It is concluded that chronic treatment with cilazapril decreases arterial blood pressure more than acute treatment. This effect seems to be due to a greater peripheral vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)
摘要
  1. 在自发性高血压大鼠中评估了新型血管紧张素转换酶(ACE)抑制剂西拉普利急性和慢性治疗对外周血管系统及肾脏排泄功能的影响。采用放射性微球技术测量局部血流量和心输出量。2. 急性治疗(静脉注射3毫克/千克)使平均动脉血压从171±7毫米汞柱降至140±7毫米汞柱(P<0.001),慢性治疗(每日口服1×10毫克/千克,共9周)使平均动脉血压从191±5毫米汞柱降至122±3毫米汞柱(P<0.001)。两种治疗方式下心输出量均未改变。慢性治疗时心率略有下降(-9%,P<0.05)。急性给药时,西拉普利的主要作用是降低肾血管阻力(-41%,P<0.001),同时分配到肾脏的心输出量比例增加(+46%,P<0.001)。长期给药时,西拉普利降低了除心脏外大多数外周血管床的局部血管阻力。3. 高剂量西拉普利(口服10毫克/千克)急性和慢性治疗均增加了尿量(分别增加107%和92%,P<0.001)和尿钠排泄(分别增加124%和111%,P<0.001),尿钾排泄略有增加。然而,低剂量(口服1毫克/千克)时肾脏仅对慢性治疗有反应。4. 得出结论,西拉普利慢性治疗比急性治疗更能降低动脉血压。这种作用似乎是由于更大程度的外周血管舒张。(摘要截选至250词)

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