Evidence for an alpha-1 receptor-mediated central sympathoinhibitory action of ketanserin

The effect of the serotonin receptor antagonist ketanserin on sympathetic nervous discharge recorded from the inferior cardiac and splanchnic nerves was studied in the baroreceptor-denervated cat. Intravenous ketanserin (0.05-0.8 mg/kg) produced dose-dependent decreases in mean arterial pressure, heart rate and sympathetic nervous discharge, with maximal decreases of 41, 7 and 55% of control, respectively. The decrease in mean arterial pressure could not be disassociated from a decrement in the pressor response to i.v. phenylephrine. The central sympatholytic effect of ketanserin was augmented in serotonin-depleted animals. In contrast, the centrally mediated reduction in sympathetic nervous discharge produced by ketanserin was blocked completely in catecholamine-depleted cats. In addition, the central sympatholytic action of the alpha-1 adrenergic receptor antagonist prazosin was blocked in catecholamine-depleted animals. These data indicate that ketanserin acts at central alpha-1 adrenergic receptors to reduce sympathetic outflow from the central nervous system. Central serotonergic pathways do not appear to be involved in the sympatholytic action of ketanserin. The nature of the interaction between central noradrenergic neurons and neurons involved in the genesis of sympathetic nerve activity is discussed.