The effects of the intracerebroventricular administration of cimetidine on hemodynamics in conscious rats: relation to the sympathetic nervous system

Abstract

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)