Ishizaki M, Kuroda K, Kajiwara N
Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Nihon Naibunpi Gakkai Zasshi. 1989 May 20;65(5):473-82. doi: 10.1507/endocrine1927.65.5_473.
Histamine H2-receptor antagonists administered into the central nervous system have been shown to increase arterial pressure (AP) in anaesthetized animals (Paakkari et al., 1982). Few studies have been reported on the effects of centrally administered cimetidine (CIM), one of the histamine H2-receptor antagonists, in conscious animals. However, the mechanism of the pressor action of histamine H2-receptor antagonists remains unclear. The present study was designed to investigate the hemodynamic effects of intracerebroventricular (i.c.v.) CIM and the interaction between the sympathetic nervous system and histamine receptor system in conscious rats. Male Wistar rats weighing 200 gr were prepared for the experiment under a conscious and minimally restricted state. Five micrograms of i.c.v. saline (SAL-ICV group, n = 5) did not produce significant changes in mean arterial pressure (MAP) or heart rate (HR) (MAP from 85.6 +/- 3.4 to 86.0 +/- 4.3 mmHg and HR from 395.0 +/- 13.9 to 395.2 +/- 8.2 bpm, respectively). Twenty micrograms of i.c.v. phenoxybenzamine (POB-ICV group, n = 6) decreased MAP from 95.8 +/- 4.1 to 85.2 +/- 3.1 mmHg, -10.7 +/- 2.2 mmHg as delta MAP, and increased HR from 392.5 +/- 8.5 to 435.3 +/- 13.9 bpm, +42.8 +/- 6.8 bpm as delta HR. Two-hundred micrograms of intravenous (i.v.) POB (POB-IV group, n = 5) also decreased MAP from 96.0 +/- 4.3 to 71.0 +/- 5.1 mmHg, -25.0 +/- 2.7 mmHg as delta MAP, and increased HR from 395.8 +/- 10.5 to 473.0 +/- 12.4 bpm, +77.2 +/- 7.6 bpm as delta HR. The changes in MAP and HR were much greater in the POB-IV group than those in the other two groups. The subsequent i.c.v. administration of 250 micrograms of CIM induced an increase in MAP (+19.4 +/- 1.7 mmHg as delta MAP) and a decrease in HR (-36.4 +/- 3.1 bpm as delta HR) in the SAL-ICV group, which continued for at least 30 minutes producing peak effects 2 minutes after i.c.v. administration of CIM. However, an elevation of MAP caused by i.c.v. CIM was much more inhibited in the POB-ICV group than in the POB-IV group (+2.5 +/- 0.7 mmHg as delta MAP in the POB-ICV group and +5.0 +/- 1.3 mmHg as delta MAP in the POB-IV group, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)
已证实，向中枢神经系统注射组胺H2受体拮抗剂可使麻醉动物的动脉血压（AP）升高（帕卡里等人，1982年）。关于组胺H2受体拮抗剂之一西咪替丁（CIM）对清醒动物的影响，报道的研究较少。然而，组胺H2受体拮抗剂的升压作用机制仍不清楚。本研究旨在探讨脑室注射（i.c.v.）CIM对清醒大鼠的血流动力学影响，以及交感神经系统与组胺受体系统之间的相互作用。对体重200克的雄性Wistar大鼠在清醒且限制最小的状态下进行实验准备。5微克的i.c.v.生理盐水（生理盐水脑室注射组，n = 5）未使平均动脉压（MAP）或心率（HR）产生显著变化（MAP分别从85.6±3.4 mmHg变为86.0±4.3 mmHg，HR从395.0±13.9次/分钟变为395.2±8.2次/分钟）。20微克的i.c.v.酚苄明（酚苄明脑室注射组，n = 6）使MAP从95.8±4.1 mmHg降至85.2±3.1 mmHg，MAP变化量为-10.7±2.2 mmHg，并使HR从392.5±8.5次/分钟升至435.3±13.9次/分钟，HR变化量为+42.8±6.8次/分钟。200微克的静脉注射（i.v.）酚苄明（酚苄明静脉注射组，n = 5）也使MAP从96.0±4.3 mmHg降至71.0±5.1 mmHg，MAP变化量为-25.0±2.7 mmHg，并使HR从395.8±10.5次/分钟升至473.0±12.4次/分钟，HR变化量为+77.2±7.6次/分钟。酚苄明静脉注射组MAP和HR的变化比其他两组大得多。随后，在生理盐水脑室注射组中，脑室注射250微克CIM导致MAP升高（MAP变化量为+19.4±1.7 mmHg）和HR降低（HR变化量为-36.4±3.1次/分钟），这种变化持续至少30分钟，在脑室注射CIM后2分钟产生峰值效应。然而，酚苄明脑室注射组中由脑室注射CIM引起的MAP升高比酚苄明静脉注射组受到的抑制要大得多（酚苄明脑室注射组MAP变化量为+2.5±0.7 mmHg，酚苄明静脉注射组MAP变化量为+5.0±1.3 mmHg）。（摘要截断于400字）
