Department of Medicine, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA
We examined the role of I
1-imidazoline (I
1-IR) receptors in
control of airway function, by testing the effects of systemic
administration of the I
1-IR agonist moxonidine on reflex responses
of tracheal smooth muscle (TSM) tone to either lung deflation
or mechanical stimulation of intrapulmonary rapidly adapting
receptors. Experiments were performed in either
-chloralose
anesthetized or decorticate, paralyzed, and mechanically ventilated
beagle dogs. Moxonidine (10 - 100 µg/kg) administered
via three different routes (femoral vein, muscular branch of
superior thyroid artery, and vertebral artery) attenuated TSM
responses to stimulation of airway sensory nerve fibers by two
different ways and caused a decrease in arterial pressure and
heart rate. These effects were dose dependent and were significantly
reversed by efaroxan (an I
1-IR and
2-adrenergic blocker) administered
via the vertebral artery. Intravertebral efaroxan abolished
the hemodynamic effects of moxonidine. Intravenous moxonidine
(10 - 100 µg/ kg) did not alter airway smooth muscle responses
to electrical stimulation of the peripheral vagus nerve. In
addition,
in vitro moxonidine (1 - 100 µg/ml) had no effect
on contractile responses to increasing doses of acetylcholine.
These findings indicate that moxonidine may act at a central
site to suppress reflex airway constriction, even when given
into the systemic circulation. Given the presence of I
1-IR sites
and
2-adrenergic receptors in brain regions participating in
airway reflexes, these receptor classes may be involved in brainstem
control of the cholinergic outflow to the airways.
