Effect of Ketanserin on Adrenal Sympathetic Nerve Activity in Rats

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Abstract
The present study was undertaken to clarify the site for the sympathoinhibitory action of ketanserin in anesthetized rats. Intravenous (i.v.) administration of ketanserin (0.5 and 5 mg/kg) produced a decrease in preganglionic adrenal sympathetic nerve activity (ANA) that is accompanied with hypotension and bradycardia. Intracerebroventricular (i.c.v.) administration of ketanserin (200 .mu.g/rat) also decreased ANA, blood pressure (BP) and heart rate (HR). Intrathecal (i.t.) administration of ketanserin (200 .mu.g/rat), on the other hand, affected neither ANA, BP nor HR. These results indicates that the site of the sympathoinhibitory action of ketanserin is the supraspinal structures, and not at the spinal cord level. In addition, the decrease in ANA after i.v. administration of ketanserin (0.5 and 5 mg/kg) was attenuated significantly with pretreatment of 5,7-dihydroxytryptamine (200 .mu.g/rat, i.c.v.) or 6-hydroxydopamine (200 .mu.g/rat, i.c.v.). These findings suggest that the adrenal sympathoinhibitory action of ketanserin may be centrally mediated via both serotonergic and noradrenergic pathways in rats.