Association of nicotinic acetylcholine receptors with central respiratory control in isolated brainstem-spinal cord preparation of neonatal rats

Nicotine exposure is a risk factor in several breathing disorders Nicotinic acetylcholine receptors (nAChRs) exist in the ventrolateral medulla, an important site for respiratory control. We examined the effects of nicotinic acetylcholine neurotransmission on central respiratory control by addition of a nAChR agonist or one of various antagonists into superfusion medium in the isolated brainstem-spinal cord from neonatal rats. Ventral C4 neuronal activity was monitored as central respiratory output, and activities of respiratory neurons in the ventrolateral medulla were recorded in whole-cell configuration. RJR-2403 (0.1-10mM), a4b2 nAChR agonist induced dose-dependent increases in respiratory frequency. Non-selective nAChR antagonist mecamylamine (0.1-100mM), a4b2 antagonist dihydro-b-erythroidine (0.1-100mM), a7 antagonist methyllycaconitine (0.1-100mM), and a-bungarotoxin (0.01-10mM) all induced dose-dependent reductions in C4 respiratory rate. We next examined effects of 20mM dihydro-b-erythroidine and 20mM methyllycaconitine on respiratory neurons. Dihydro-b-erythroidine induces hyperpolarization and decreases intraburst firing frequency of inspiratory and preinspiratory neurons. In contrast, methyllycaconitine has no effect on the membrane potential of inspiratory neurons, but does decrease their intraburst firing frequency while inducing hyperpolarization and decreasing intraburst firing frequency in preinspiratory neurons. These findings indicate that a4b2 nAChR is involved in both inspiratory and preinspiratory neurons, whereas a7 nAChR functions only in preinspiratory neurons to modulate C4 respiratory rate.

Respiratory centre sensitivity and exercise tolerance in healthy Thais.

To determine the range of normal values of respiratory centre sensitivity and exercise tolerance in Thais, 69 healthy subjects, 18 to 72 years of age, participated in a series of tests, i.e. ventilatory drive, ventilatory response, musculo-ventilation transfer and the two-minute walking test with rating of the breathing sensation on a visual analogue scale. Our results showed higher end-tidal Pco2 and tidal volume response to CO2 and less exercise tolerance in the elderly than in the young. Only in young males was the ventilatory response to CO2 higher than in females. No attempt has yet been made to explain the lower ventilatory response in Thais as compared with Americans. Apparently, the defective respiratory apparatus, viz. increased airways resistance and not the blunting of respiratory centre sensitivity, contributes principally to relative hypoventilation and exercise limitation in the elderly. The compensation, with high tidal volume response to CO2, seems ineffective in maintaining normo-ventilation.

Cambios respiratorios centrales por salbutamol en pacientes asmáticos / Central respiratory changes by Salbutamol in asthmatic patients

La acción broncodilatadora del Salbutamol ha sido plenamente demostrada en la práctica médica, particularmente en el tratamiento de la crisis asmáticas. Se plantea, por otra parte, en trabajos recientes, algunas acciones del medicamento a nivel del sistema nervioso central, así como una mayor efectividad cuando se combinan la terapéutica oral e inhalatoria que cuando es administrada la droga por una de estas vías por separado. El paciente asmático tiene una retención crónica de CO2 lo cual se acompaña de una disminución de la sensibilidad del centro respiratorio a la hipercapnea. Se tomó una muestra de 50 personas del sexo masculino, de los que 20, forman el grupo control y 30 son asmáticos. se les realizó una prueba de respiración en circuito cerrado antes y después de la administración de la droga por vía oral e inhalatoria. Se concluyó, después de efectuada la investigación, que el salbutamol ejerce una acción estimuladora sobre el centro respiratorio, lo cual se manifiesta con la administración de la droga por vía oral en pacientes asmáticos