The Effects of Ketanserin on Hemodynamic Response after Intracerebroventricular Administration of 5-Hydroxytryptamine

Abstract

Recently, the serotonergic nervous system has been receiving attention, as it participates in the hemodynamic regulation as well as in the pathogenesis of hypertension. The purpose of this experiment is to investigate the role of the central and peripheral seroto-nergic receptor in the hemodynamic responses induced by intracerebroventricular (i.c.v) administration of 5-hydroxytryptamine (5-HT).
Eight week-old male spontaneously hypertensive rats (SHR) and age matched Wistar Kyoto rats (WKY) were used, and the experiment was performed under conscious and minimumly restrained states. Five pg of 5-HT was given i.c.v. followed by i.c.v. administration of 200μg ketanserin. Mean arterial pressure (MAP) and heart rate (HR) were observed continuously for 30 minutes. Then 5μg of 5-HT was given i.c.v. again in the same rat (SHR -IC group, n = 7; WKY-IC group, n = 7). The rest of the rats received 200pg of ketanserin intravenously (i.v.) after i.c.v. administration of 5pg 5-HT, and the same amount of 5-HT was given i.c.v. after the ketanserin i.v. (SHR-IV group, n =7; WKY-IV group, n =6).
Five-HT elicited a significant pressor response in all groups of rats and a slight nonsignificant increase in HR. In SHR-IC group and WKY-IC group, neither ketanserin i.c.v. nor the second 5-HT i.c.v. administration caused significant changes in MAP and HR. In SHR -IV group, i.v. ketanserin caused a significant decrease in MAP (-8.8 ± 1.4mmHg), but no significant change in MAP in WKY-IV group (-1.1 ± 1.2mmHg). There was a significant increase in MAP after the second i.c.v. administration of 5-HT in SHR-IV group (+26.7 ± 4.1mmHg) and in WKY-IV group (+19.0 ± 1.8mmHg).
Ketanserin is a selective S2 receptor antagonist, and our data indicating that the pressor response to i.c.v. 5-HT administration was abolished by i.c.v. pretreatment with ketanserin and not by the i.v. pretreatment of the drug suggest that the central S2 receptor plays an important role in the hemodynamic change after i.c.v. administration of 5-HT. Although individual variations of HR responses were large, the significant decrease in HR after the i.v. administration of ketanserin may suggest that the serotonergic nervous system participates in the heart rate-controlling mechanism. Since i.v. ketanserin administration caused a significant depressor response in SHR but not in WKY, the peripheral serotonergic nervous system may play a role in the hemodynamic regulation and the pathogenesis of hypertension in SHR.