意識下ラットにおける脳室内セロトニン投与による血行動態の変化:セロトニン受容体および交感神経系の関与について

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We have previously reported that the intracerebroventricular (i.c.v.) administration of 5-hydroxytryptamine (5-HT) in conscious rats elicited significant pressor response, which was accompanied with an increase in plasma norepinephrine and the pressor response, was abolished by peripheral phenoxybenzamine pretreatment. For further investigation of the relationship between the serotonergic nervous system and the sympathetic nervous system, the effect of either i.c.v. or intravenous (i.v.) serotonin receptor antagonist, methysergide pretreatment on hemodynamic response to centrally administrated 5-HT was studied.<BR>Male Wistar rats weighing approximately 250g were used. On the day before the study, the unilateral carotid artery was cannulated (PE-50) to facilitate mean arterial pressure (MAP) and pressure triggered heart rate (HR) observation. Also, a cannula (PE-10) was inserted stereotaxically into the anterior horn of the lateral cerebral ventricle. The experiment was performed under a conscious and minimumly restrained state. After the observation of resting MAP and HR for at least 20 minutes, 5μg of 5-HT was given i.c.v. and MAP and HR were recorded for 50 minutes. Then, the rats were divided into two groups, one group (n=9) received 1μg of i.c.v. methysergide and the other group (n=10) received 1 mg/kg of i.v. methysergide. Ten minutes after either methysergide i.c.v. or i.v. treatment, 5μg of 5-HT was administrated i.c.v. again, and MAP and HR were observed for 30 minutes. Resting MAP and HR were 101.6 ± 3.0mmHg and 413.8 ± 20.0/min, respectively. Whereas i.c.v. 5-HT elicited a consistent pressor response and decrease in HR 2 minutes after the administration (+28.2±3.3mmHg and -40.5 ± 8.6/min, respectively), there was no significant change in MAP and HR with i.c.v. 5-HT administration after the pretreatment with methysergide either by i.c.v. (-1.1 ± 3.3mmHg and +28.1 ± 12.3/min, respectively) or i.v. (+5.0 ± 2.9 mmHg and -4.0 ± 12.4/min, respectively).<BR>Since methysergide is a serotonin receptor antagonist, the observed effects of methysergide on 5-HT induced pressor response suggest that this pressor response is evoked by the stimulation of the serotonergic nervous system. It has been suggested that i.c.v. administrated 5-HT could nonspecifically stimulate the sympathetic system, but this may not be a feasible mechanism of the pressor effect of centrally administrated 5-HT. It is not clear whether the effect of systemically administrated methysergide resulted from the inhibition of the peripheral serotonin receptor or from the central penetration of the agent.<BR>These data suggest that the serotonergic nervous system is subserving as a pressor mechanism in rats and the sympathetic nervous system is closely related to the serotonergic nervous system.
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意識下ラットにおける脳室内セロトニン投与による血行動態の変化:セロトニン受容体および交感神経系の関与について

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