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特拉唑嗪对清醒动物倾斜时血压反应的影响:与哌唑嗪的比较

[Effects of terazosin on the blood pressure responses to tilting in conscious animals: comparison with prazosin].

作者信息

Bessho H, Hara Y, Kimura Y, Narimatsu A, Horii D, Tobe A

机构信息

Pharmaceuticals Laboratory, Mitsubishi Chemical Industries, Ltd., Yokohama, Japan.

出版信息

Nihon Yakurigaku Zasshi. 1988 May;91(5):275-83. doi: 10.1254/fpj.91.275.

Abstract

Inhibitory effects of terazosin on the compensatory blood pressure responses to tilting were studied in conscious rabbits and spontaneously hypertensive rats (SHR). In rabbits, doses which reduced the mean blood pressure by 15 mmHg were 330 micrograms/kg, i.v., for terazosin and 42 micrograms/kg, i.v., for prazosin, while those which depressed the blood pressure responses to tilting by 30 mmHg were 180 micrograms/kg, i.v., for terazosin and 54 micrograms/kg, i.v., for prazosin. In SHR, almost equal decreases in the mean blood pressure (about 30%) were observed by 1 mg/kg prazosin, p.o., 20 mg/kg hexamethonium, i.p., 3 mg/kg hydralazine, p.o., or 3 mg/kg nicardipine, p.o. In these conditions, prazosin and hexamethonium markedly depressed the blood pressure responses to tilting, whereas hydralazine and nicardipine showed little effect. The results with these antihypertensive drugs closely paralleled the established orthostatic profiles seen clinically. In this SHR tilting model, when the mean blood pressure was reduced by 15%, prazosin significantly depressed the tilting reflexes; however, terazosin produced no depression. Considering the dose ratio of terazosin to prazosin for antihypertensive effects and inhibitory effects on the tilting reflexes, the orthostatic liability of terazosin was about 3 times as low as that of prazosin. On the basis of these results, it is expected that terazosin causes less orthostatic hypotension than prazosin in clinical use.

摘要

在清醒家兔和自发性高血压大鼠(SHR)中研究了特拉唑嗪对倾斜引起的代偿性血压反应的抑制作用。在家兔中,静脉注射特拉唑嗪使平均血压降低15 mmHg的剂量为330微克/千克,静脉注射哌唑嗪的剂量为42微克/千克,而静脉注射特拉唑嗪使对倾斜的血压反应降低30 mmHg的剂量为180微克/千克,静脉注射哌唑嗪的剂量为54微克/千克。在SHR中,口服1毫克/千克哌唑嗪、腹腔注射20毫克/千克六甲铵、口服3毫克/千克肼屈嗪或口服3毫克/千克尼卡地平可使平均血压出现几乎相同程度的下降(约30%)。在这些情况下,哌唑嗪和六甲铵显著抑制了对倾斜的血压反应,而肼屈嗪和尼卡地平的作用很小。这些抗高血压药物的结果与临床上已确立的直立性特征密切平行。在这个SHR倾斜模型中,当平均血压降低15%时,哌唑嗪显著抑制倾斜反射;然而,特拉唑嗪没有产生抑制作用。考虑到特拉唑嗪与哌唑嗪在抗高血压作用和对倾斜反射的抑制作用方面的剂量比,特拉唑嗪的直立性不良反应约为哌唑嗪的三分之一。基于这些结果,预计在临床使用中特拉唑嗪引起的直立性低血压比哌唑嗪少。

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