ABSTRACT
Cough, the main airway defensive process, is modulated by multiple sensory inputs from the respiratory system and outside of it. This modulation is one of the mechanisms that contributes to the sensitization of cough pathways at the peripheral and/or central level via neuroplasticity and it manifests most often as augmented coughing. Cardiorespiratory coupling is an important mechanism responsible for a match between oxygenation and cardiac output and bidirectional relationships exist between respiration and cardiovascular function. While the impact of cough with the robust swings of the intrathoracic pressure on haemodynamic parameters and heart electrophysiology are well characterized, little is known about the modulation of cough by haemodynamic parameters - mainly the blood pressure. Some circumstantial findings from older animal studies and more recent sophisticated analysis confirm that baroreceptor stimulation and unloading alters coughing evoked in experiments. Clinical relevance of such findings is not presently known.
Subject(s)
Cough , Pressoreceptors , Animals , Baroreflex , Blood Pressure , Cardiac Output , Heart Rate , RespirationABSTRACT
We studied the effects of GABA receptor agonists microinjections in medullary raphé on the mechanically induced tracheobronchial cough response in anesthetized, unparalyzed, spontaneously breathing cats. The results suggest that GABA-ergic inhibition significantly contributes to the regulation of cough reflex by action of both GABA(A) and GABA(B) receptors. The data are consistent with inhomogeneous occurrence of GABA-ergic neurons in medullary raphé and their different involvement in the cough reflex control. Cells within rostral nucleus raphéobscurus with dominant role of GABA(A) receptors and neurons of rostral nucleus raphépallidus and caudal nucleus raphémagnus with dominant role of GABA(B) receptors participate in regulation of cough expiratory efforts. These cough control elements are distinct from cough gating mechanism. GABA-ergic inhibition in the raphé caudal to obex had insignificant effect on cough. Contradictory findings for GABA, muscimol and baclofen administration in medullary raphé suggest involvement of coordinated activity of GABA on multiple receptors affecting raphé neurons and/or the local neuronal circuits in the raphé modulating cough motor drive.
Subject(s)
Cough/physiopathology , Medulla Oblongata/physiology , Raphe Nuclei/physiology , Receptors, GABA-A/physiology , Receptors, GABA-B/physiology , Reflex/physiology , Animals , Baclofen/pharmacology , Baclofen/therapeutic use , Cats , Cough/drug therapy , GABA-A Receptor Agonists/pharmacology , GABA-A Receptor Agonists/therapeutic use , GABA-B Receptor Agonists/pharmacology , GABA-B Receptor Agonists/therapeutic use , Medulla Oblongata/drug effects , Muscimol/pharmacology , Muscimol/therapeutic use , Raphe Nuclei/drug effects , Reflex/drug effectsABSTRACT
GABA, muscimol, and baclofen were microinjected into the rostral (rNTS) and caudal solitary tract nucleus (cNTS) in 24 anesthetized cats. Electromyograms (EMGs) of diaphragm (DIA) and abdominal muscles (ABD), blood pressure and esophageal pressure (EP) were recorded and analysed. Bilateral microinjections of 1â¯mM GABA (total 66⯱â¯4â¯nl), 1â¯mM baclofen (64⯱â¯4â¯nl) and unilateral microinjections of 0.5â¯mM muscimol (33⯱â¯1â¯nl) in the rNTS significantly reduced cough number (CN), amplitudes of ABD EMGs, expiratory EP, and prolonged the duration of the cough inspiratory phase. GABA microinjections decreased the amplitudes of cough-related DIA EMGs and inspiratory EP; muscimol microinjections decreased the cough DIA EMG on the contralateral side. Only microinjections of GABA into the cNTS suppressed CN. In some cases, microinjections prolonged the inspiratory phase, lowered respiratory rate, changed the depth of breathing, and increased blood pressure and heart rate. Our results confirm that GABA-ergic inhibitory mechanisms in the rNTS can regulate coughing in the anesthetized cat.