EVIDENCE FOR A CENTRAL SYMPATHOEXCITATORY ACTION OF ALPHA-2 ADRENERGIC ANTAGONISTS

Abstract

The effect of .alpha.2-adrenergic receptor antagonists on sympathetic nerve discharge (SND) recorded from the external carotid and splanchnic nerves was studied in baroreceptor-denervated cats. Low i.v. doses of piperoxane and rauwolscine dramatically increased SND and produced a concomitant rise in mean arterial pressure and heart rate. High doses of piperoxane resulted in an increase in SND. High doses of rauwolscine markedly reduced mean arterial pressure, heart rate and SND. The pressor response to i.v. norepinephrine was greatly attenuated by high doses of rauwolscine and slightly reduced by piperoxane. Piperoxane failed to alter SND in catecholamine-depleted animals. In vitro binding experiments indicated that piperoxane and rauwolscine bound selectively to the .alpha.2-adrenergic receptor and had little affinity for .alpha.1-receptor sites. Rauwolscine displaced [3H]LSD binding. Low doses of the .alpha.2-receptor antagonist piperoxane and rauwolscine evidently act centrally to increase SND. The nature of the interactions between central noradrenergic neurons and neurons involved in the genesis of sympathetic nerve activity is discussed.