title: gamma-Aminobutyric acid contributes to modulation of cardiorespiratory control after chronic ventilatory loading.
abstract: Diseases imposing chronic ventilatory loads may depress ventilation and cause chronic hypercapnia. This may be a result of mechanical loading imposed on pre-existing decreased respiratory drive or functional alteration of neural circuits involved in ventilatory control. To evaluate these possibilities, chronic resistive airway loading was imposed in rats via a circumferential tracheal band which tripled tracheal resistance (obstructed group). Sham surgery was performed in controls. After 8 weeks, animals were anesthetized (urethane) and tracheostomy performed relieving increased tracheal resistance. The ventral medullary surface (VMS) was exposed and the intermediate area (IA) identified. The integrated diaphragm EMG (EMGDI) was recorded. The obstructed group was hypercapnic while controls were eucapnic (PCO2, 45.1 +/- 7.9 vs. 37.6 +/- 3.4 Torr; P < 0.001). Respiratory rate (RR) remained lower in obstructed than in control animals despite relief of the resistive load by tracheostomy (58.5 +/- 5.1 vs. 75.4 +/- 5.4 bpm; P < 0.05). Application of 1 mM bicuculline soaked pledgets (BIC) to the IA of the VMS significantly increased EMGDI in obstructed but not in control animals (27.5 +/- 5.5 vs. 5.2 +/- 4.4%; P < 0.006). RR was unaffected. Mean arterial pressure increased with BIC in obstructed but not control animals (23.0 +/- 6.5 vs. 4.5 +/- 3.5%; P < 0.02). These data suggest that alteration of cardiorespiratory control occurs during chronic resistive hypercapnic loading and that GABAergic neurons in the VMS participate in this adaptive response.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Long Island Jewish Medical Center, Albert Einstein College of Medicine, New Hyde Park, NY 11040, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Rao
authors.forename: H E
authors.initials: HE
authors.lastname: Greenberg
authors.forename: A L
authors.initials: AL
authors.lastname: Sica
authors.forename: S M
authors.initials: SM
authors.lastname: Scharf
mesh_terms: D000402:Airway Obstruction / Q000150:complications; D000403:Airway Resistance; D000818:Animals; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects; D004576:Electromyography; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects / Q000502:physiology*; D015656:Respiratory Mechanics / Q000187:drug effects* / Q000502:physiology; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000187:drug effects; D014132:Trachea / Q000502:physiology / Q000601:surgery; D014139:Tracheostomy; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D005680:gamma-Aminobutyric Acid