The present
results suggest that the acute hypotensive action of moxonidine is due predominantly if not exclusively to
its a2-AR
agonist properties. Thus, our data
provide no support to the theory that this drug might work via imidazoline receptors in RVL .
C1 and other
bulbospinal neurons are mildly inhibited by a2-AR agonists via a postsynaptic mechanism involving opening
of a barium-sensitive potassium current.
Further inhibition of these neurons occurs via presynaptic inhibition of glutamate release. In combination,
these two mechanisms probably account for the bulk of the powerful
sympathoinhibition produced by centrally acting antihypertensive agents in RVL.
However, a2-AR agonists (like µ opioid receptor agonists) do not produce
purely inhibitory
effects on bulbospinal RVL neurons because they also reduced the strength of GABAergic inputs
to these cells. The functional significance
of the simultaneous decrease in GABA and glutamate release by a2-AR and µ opioid agonists remains to be
elucidated.