I-1-IMIDAZOLINE RECEPTORS AND CHOLINERGIC OUTFLOW TO THE AIRWAYS

We examined the role of I-1-imidazoline receptors in the control of ai rway function, by testing the effects of systemic administration of th e I-1-imidazoline agonist moxonidine on reflex responses of tracheal s mooth muscle (TSM) tone to either lung deflation or mechanical stimula tion of intrapulmonary rapidly adapting receptors. Experiments were pe rformed in either alpha-chloralose anaesthetized or decorticate, paral yzed and mechanically ventilated beagle dogs. Moxonidine (10-100 mu g/ kg) administered via three different routes (the femoral vein, muscula r branch of superior thyroid artery, and vertebral artery) attenuated TSM responses to stimulation of airway sensory nerve fibers by two dif ferent ways, and caused a decrease in arterial pressure and heart rate . These effects were dose-dependent, and were significantly reversed b y efaroxan (an I-1-imidazoline and alpha(2)-adrenergic blocker) admini stered via the vertebral artery. Intravertebral efaroxan abolished the hemodynamic effects of moxonidine. Intravenous moxonidine (10-100 mu g/kg) did not alter airway smooth muscle responses to electrical stimu lation of the peripheral vagus nerve. In addition, in vitro moxonidine (1-100 mu g/ml) had no effect on contractile responses to increasing doses of acetylcholine. These findings indicate that moxonidine may ac t at a central site to suppress reflex airway constriction, even when given into the systemic circulation Given the presence of I-1-imidazol ine sites and alpha(2)-adrenergic receptors in brain regions participa ting in airway reflexes, these receptor classes may be involved in bra instem control of the cholinegic outflow to the airways. (C) 1998 Publ ished by Elsevier Science B.V. All rights reserved.