Centrally acting antihypertensive drugs
with an imidazoline structure, like clonidine and moxonidine, are effective for treatment of
moderate to severe forms
of hypertension. The main site of action of these drugs is thought to be RVL.
However, their molecular and synaptic
mechanisms of action at this level are controversial. In particular, it is
unclear whether the sympathoinhibition evoked by these drugs is mediated via a2-adrenoceptors or the proposed I1-imidazoline receptors.
a2-ARs are present in RVL bulbospinal
neurons as shown by immunocytochemical
studies. Their stimulation activates an inwardly rectifying potassium current of small
amplitude.
This latter observation prompted us to
test the hypothesis that a presynaptic modulation of transmitter release in RVL
could better explain the hypotensive actions of a2-AR agonists and imidazoline compounds.