Moxonidine acting centrally inhibits airway reflex responses.
We examined the role of I1-imidazoline (I1-IR) receptors in control of airway function, by testing the effects of systemic administration of the I1-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 alpha-chloralose anesthetized or decorticate, paralyzed, and mechanically ventilated beagle dogs. Moxonidine (10-100 micrograms/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 I1-IR and alpha 2-adrenergic blocker) administered via the vertebral artery. Intravertebral efaroxan abolished the hemodynamic effects of moxonidine. Intravenous moxonidine (10-100 micrograms/kg) did not alter airway smooth muscle responses to electrical stimulation of the peripheral vagus nerve. In addition, in vitro moxonidine (1-100 micrograms/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 I1-IR sites and alpha 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.
Department of Medicine, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA. mah10@po.cwru.edu
M A
MA
Haxhiu
I A
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Dreshaj
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CB
McFadden
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Erokwu
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P
Ernsberger
D000109:Acetylcholine / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003655:Decerebrate State; D004285:Dogs; D004525:Efferent Pathways / Q000502:physiology; D004558:Electric Stimulation; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D054755:Imidazoline Receptors; D066298:In Vitro Techniques; D008168:Lung / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D009412:Nerve Fibers / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology; D011955:Receptors, Drug / Q000819:agonists / Q000502:physiology*; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D014132:Trachea / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D014630:Vagus Nerve / Q000502:physiology
D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D001572:Benzofurans; D007093:Imidazoles; D054755:Imidazoline Receptors; D011955:Receptors, Drug; C043482:moxonidine; C062597:efaroxan; D000109:Acetylcholine