The Role of the Sympathetic Nervous System and Adrenals in Hemodynamic Changes after Intracerebroventricular

Administration of 5-Hydroxytryptamine in Rats

Abstract

Recently, the role of the serotonergic nervous system has been implicated in blood pressure regulation and in the pathogenesis of hypertension. However, the effects of 5-hydroxytryptamine (5-HT) administration on hemodynamics have been notoriously inconsistent and the precise mechanism of the blood pressure regulation of the serotonergic nervous system has not been elucidated yet. In our previous study, we demonstrated that the intracerebroventricular (i.c.v.) administration of 5-HT in rats elicited consistent pressor response with concomitant increase in plasma norepinephrine and that the pressor response was abolished by systemic pretreatment of phenoxybenzamine or by serotonin receptor antagonist, methysergide. The purpose of this experiment is to investigate further the relationship between the sympathetic nervous system and the serotonergic nervous system.
MATERIALS AND METHODS : Male Wistar rats weighing approximately 200g were used. A cannula was inserted stereotaxically into the anterior horn of the lateral cerebral ventricle. According to the experimental protocol, the rats were divided into 3 groups. One group of rats received 6-hydroxydopamine (6-OHDA) from the tail vein at the dose of 200mg/kg each on 10, 2 and 1 day before the experiment (6-OHDA i.v. group, n = 16). The rats of the control group received saline alone (6-OHDA i.v. control group, n= 19). Another group of rats received i.c.v. 6-OHDA at the dose of 200 pg each on 2 and 1 day before the experiment (6-OHDA i.c.v. group, n = 6) and the control rats received saline alone (6-OHDA i.c.v. control group, n = 8). The remaining group of rats were subjected to bilateral adrenalectomy under ether anesthesia 24 hours before the experiment (Adx group, n= 8) and the control rats were subjected to sham adrenalectomy (Sham adx group, n= 6). In all rats, a cannula was inserted into the carotid artery on the day before the experiment. The experiment was performed under conscious state with the exception of those received i.c.v. 6-OHDA that showed extreme restlessness. After the resting observation of at least 20 minutes, 5 μg of 5-HT were given i.c.v. and mean arterial pressure (MAP) as well as heart rate (HR) were observed for about 20 minutes.
RESULTS : Resting MAP and HR of the 6-OHDA i.v. group did not differ significantly from those of the 6-OHDA i.v. control group (101.8±1.7 mmHg, 428.7±15.7 bpm and 102.8±2.3 mmHg, 414.4±10.4 bpm, respectively). Whereas i.c.v. 5-HT elicited significant pressor response and decrease in HR at 2 minutes after the administration in the 6-OHDA i.v. control group (+29.9±2.6 mmHg and -46.0±8.2 bpm, respectively), both pressor response and decrease in HR were significantly suppressed in the 6-OHDA i.v. group (+15.6±4.2 mmHg and -5.0±6.4 bpm, respectively). There were no significant difference in resting MAP and HR between the 6-OHDA i.c.v. control group and the 6-OHDA i.c.v. group. I.c.v. 5-HT administration elicited significant pressor response (+28.6±3.7 mmHg) and decrease in HR (-44.3±8.7 bpm) in the 6-OHDA i.c.v. control group, however, there were no significant changes in MAP and HR in the 6-OHDA i.c.v. group (+3.3±1.6 mmHg and -20.0±16.5 bpm, respectively). In the Adx group, resting MAP and HR did not differ significantly from those of the Sham adx group (98.1±3.7 mmHg, 455.0±20.7 bpm, 102.5±4.7 mmHg and 403.3±13.0 bpm, respectively). Pressor response and decrease in HR at 2 minutes after the i.c.v. 5-HT were significant and similar in those two groups (+25.0±3.4 mmHg, -40.4±17.4 bpm in the Adx group and +23.3±2.7 mmHg, -43.3±12.2 bpm in the Sham adx group). DISCUSSION AND CONCLUSIONS : Since i.c.v. administration of 5-HT elicited pressor response and the change was significantly suppressed either by i.v. or by i.c.v. pretreatment with 6-OHDA,