Effects of ketanserin on hemodynamic changes after intracerebroventricular corticotropin releasing factor administration in rats

Abstract

In order to elucidate the relation between the serotonergic nervous system and the hypothalamus-pituitary system in hemodynamic regulation, the effects of a serotonin S2 receptor antagonist, ketanserin, on hemodynamic changes after intracerebroventricularly (i.c.v.) administrated corticotropin releasing factor (CRF) were investigated. Male Wistar rats (n = 19) weighing approximately 200 g were used. Thirty minutes after either intravenous (i.v.) (KET-IV group) or intracerebroventricular (KET-IC group) administration of 100 micrograms of ketanserin, 10 micrograms of CRF was given i.c.v. and mean arterial pressure (MAP) and heart rate (HR) were observed for 40 minutes, which was followed by blood sampling for plasma norepinephrine (PNE). The experiment was performed under conscious state. Resting MAP and HR were similar in both groups. Neither i.v. or i.c.v. ketanserin alone induced significant changes in MAP and HR. Although there was consistent pressor responses (+10 +/- 1.7 mmHg) and increase in HR (+31 +/- 13 bpm) after CRF administration in KET-IV group, there was not significant changes in MAP (+17 +/- 1.0 mmHg) and HR (+4.3 +/- 5.7 bpm) in KET-IC group. PNE was significantly higher in KET-IV group than that in KET-IC group, 489 +/- 71 pg/ml and 179 +/- 57 pg/ml, respectively. These data suggest that the pressor response to i.c.v. CRF is related to the increased peripheral sympathetic tone, and that the central serotonergic nervous system may play an important role in the hemodynamic changes.