title: Suppression of the cough reflex by α 2-adrenergic receptor agonists in the rabbit.
abstract: The α 2-adrenergic receptor agonist clonidine has been shown to inhibit citric acid-induced cough responses in guinea pigs when administered by aerosol, but not orally. In contrast, oral or inhaled clonidine had no effect on capsaicin-induced cough and reflex bronchoconstriction in humans. In addition, intravenous administration of clonidine has been shown to depress fentanyl-induced cough in humans. We investigated the effects of the α 2-adrenergic receptor agonists, clonidine and tizanidine, on cough responses induced by mechanical and chemical (citric acid) stimulation of the tracheobronchial tree. Drugs were microinjected (30-50 nL) into the caudal nucleus tractus solitarii (cNTS) and the caudal ventral respiratory group (cVRG) as well as administered intravenously in pentobarbital sodium-anesthetized, spontaneously breathing rabbits. Bilateral microinjections of clonidine into the cNTS or the cVRG reduced cough responses at 0.5 mmol/L and abolished the cough reflex at 5 mmol/L. Bilateral microinjections of 0.5 mmol/L tizanidine into the cNTS completely suppressed cough responses, whereas bilateral microinjections of 5 mmol/L into the cVRG only caused mild reductions in them. Depressant effects on the cough reflex of clonidine and tizanidine were completely reverted by microinjections of 10 mmol/L yohimbine. Intravenous administration of clonidine (80-120 μg/kg) or tizanidine (150-300 μg/kg) strongly reduced or completely suppressed cough responses. These effects were reverted by intravenous administration of yohimbine (300 μg/kg). The results demonstrate that activation of α 2-adrenergic receptors in the rabbit exerts potent inhibitory effects on the central mechanism generating the cough motor pattern with a clear action at the level of the cNTS and the cVRG.
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica, Sezione Scienze Fisiologiche, Università degli Studi di Firenze Viale G.B. Morgagni 63, 50134, Firenze, Italy.
authors.forename: Elenia
authors.initials: E
authors.lastname: Cinelli
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica, Sezione Scienze Fisiologiche, Università degli Studi di Firenze Viale G.B. Morgagni 63, 50134, Firenze, Italy.
authors.forename: Fulvia
authors.initials: F
authors.lastname: Bongianni
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica, Sezione Scienze Fisiologiche, Università degli Studi di Firenze Viale G.B. Morgagni 63, 50134, Firenze, Italy.
authors.forename: Tito
authors.initials: T
authors.lastname: Pantaleo
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica, Sezione Scienze Fisiologiche, Università degli Studi di Firenze Viale G.B. Morgagni 63, 50134, Firenze, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Mutolo
keywords: Caudal nucleus tractus solitarii; caudal ventral respiratory group; clonidine; cough reflex; tizanidine; yohimbine