The Prototypical Imidazoline-1 Receptor Ligand Moxonidine Activates Alpha2-Adrenoceptors in Bulbospinal Neurons of the RVL. Abdallah Hayar and Patrice G. Guyenet. Department of Pharmacology, University of Virginia, Charlottesville, VA 22908.
APStracts 6:0506N, 1999.
Moxonidine is an antihypertensive drug which lowers sympathetic vasomotor tone by stimulating either alpha2-adrenergic ((2-AR) or imidazoline I1 receptors within the rostral ventrolateral medulla (RVL). In this study, we investigated the effects of moxonidine (10 然) on RVL neurons in brainstem slices of neonatal rats. We recorded exclusively from retrogradely labeled RVL bulbospinal neurons (putative presympathetic neurons) except for some extracellular recordings. Prazosin was used to block alpha1-adrenoceptors. Moxonidine inhibited the extracellularly recorded discharges of all spontaneously active RVL neurons tested (bulbospinal and unidentified). This effect was reversed or blocked by the selective (2-AR antagonist SKF 86466 (10 然). In contrast, the I1 imidazoline ligand AGN 192403 (10 然) had no effect on the spontaneous activity. In whole-cell recordings (holding potential -70 mV), moxonidine produced a small and variable outward current (mean 7 pA). This current was observed in both tyrosine hydroxylase-immunoreactive and other bulbospinal neurons and was blocked by SKF 86466. Excitatory postsynaptic currents (EPSCs) evoked by focal electrical stimulation were isolated by incubation with gabazine and strychnine and inhibitory postsynaptic currents (IPSCs) were isolated with CNQX. Moxonidine reduced the amplitude of the evoked EPSCs (EC50 = 1 然; 53% inhibition at 10 然) but not their decay time constant (5.6 ms). The effect of moxonidine on EPSCs persisted in barium (300 然) and was reduced about 80% by SKF 86466. Moxonidine also reduced the amplitude of evoked IPSC by 63%. In conclusion, moxonidine inhibits putative RVL presympathetic neurons both presynaptically and postsynaptically. All observed effects in the present study are consistent with an (2-AR agonist activity of moxonidine.
Received 13 July 1999; accepted in final form 6 October 1999.
APS Manuscript Number J571-9.
Article publication pending Journal of Neurophysiology.
ISSN 1080-4757 Copyright 1999 The American Physiological Society.
Published in APStracts on 21 December 1999