Characterization of the central sympathoinhibitory action of ketanserin.

The present study was designed to determine whether the central sympatholytic effects of ketanserin result from the ability of the drug to block serotonin2 or alpha-1 adrenergic receptors. Ketanserin produced a dose-related inhibition of sympathetic nerve discharge recorded from the inferior cardiac nerve in chloralose-anesthetized cats. Administration of a large dose of prazosin (1 mg/kg i.v.) decreased arterial blood pressure and inhibited sympathetic activity for several hours. Additional doses of prazosin failed to further inhibit sympathetic nerve discharge. Pretreatment with prazosin (1 mg/kg i.v.) also blocked the ability of ketanserin to inhibit sympathetic activity. Conversely, pretreatment with ketanserin blocked the central sympatholytic action of prazosin. In contrast, the alpha-2 adrenergic agonist clonidine inhibited sympathetic activity in animals pretreated with prazosin. The highly selective serotonin2 antagonist, LY 53857, failed to affect arterial blood pressure, heart rate or sympathetic activity recorded from the inferior cardiac nerve. These data, along with earlier results from our laboratory, provide strong evidence to indicate that ketanserin produces a centrally mediated inhibition of sympathetic nerve discharge as a result of the ability of the drug to block alpha-1 adrenergic receptors.