I1-imidazoline receptors and cholinergic outflow to the airways.
We examined the role of I1-imidazoline receptors in the control of airway function, by testing the effects of systemic administration of the I1-imidazoline 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 anaesthetized or decorticate, paralyzed and mechanically ventilated beagle dogs. Moxonidine (10-100 microg/kg) administered via three different routes (the 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-imidazoline and alpha2-adrenergic blocker) administered via the vertebral artery. Intravertebral efaroxan abolished the hemodynamic effects of moxonidine. Intravenous moxonidine (10-100 microg/kg) did not alter airway smooth muscle responses to electrical stimulation of the peripheral vagus nerve. In addition, in vitro moxonidine (1-100 microg/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-imidazoline sites and alpha2-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, OH 44106, USA. mah10@po.cwru.edu
M A
MA
Haxhiu
I A
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Dreshaj
C B
CB
McFadden
B O
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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; D002799:Cholinergic Fibers / Q000737:chemistry / Q000502:physiology*; D004285:Dogs; D004558:Electric Stimulation; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D054755:Imidazoline Receptors; D008465:Mechanoreceptors / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000294:innervation / Q000502:physiology; D009411:Nerve Endings / Q000737:chemistry / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D011955:Receptors, Drug / Q000819:agonists / Q000502:physiology*; D014132:Trachea / Q000294:innervation*; D014630:Vagus Nerve / Q000737:chemistry* / Q000166:cytology / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D001572:Benzofurans; D007093:Imidazoles; D054755:Imidazoline Receptors; D011955:Receptors, Drug; D014665:Vasodilator Agents; C043482:moxonidine; C062597:efaroxan; D000109:Acetylcholine