Sodium salicylate centrally augments ventilation through cholinergic mechanisms.
Several different stimuli, including hydrogen ions, may exert their effect on central ventilatory control through cholinergic mechanisms. Salicylates are known to be central respiratory stimulants. Therefore this study explored whether the ventilatory effect of sodium salicylate (SAL) is through cholinergic mechanisms. Ventriculocisternal perfusion was used in spontaneously breathing anesthetized (pentobarbital sodium, 30 mg/kg) mongrel dogs to study the effects of SAL (50 mM), atropine (ATR, 4.8 mM), and SAL-ATR on ventilation. After 15 min of perfusion with mock cerebrospinal fluid, each test agent was perfused for 15 min at a rate of 1 ml/min. Cardiovascular and ventilatory parameters were monitored. Values at 15 min of test agent perfusion were compared with values at 15 min of mock cerebrospinal fluid perfusion, with each animal used as its own control. Body temperature was kept between 37.5 and 39.0 degrees C. Perfusion with SAL increased minute ventilation (VE) by 54% (P less than 0.005) and respiratory frequency by 50% (P less than 0.005). Tidal volume was not changed, but mean inspiratory flow rate increased (P less than 0.05). Perfusion with ATR decreased VE by 22% (P less than 0.1), and perfusion with SAL-ATR decreased VE by 20% (P = 0.01). No significant cardiovascular changes were noted in any group. We conclude that SAL increases VE centrally, primarily by increasing respiratory frequency. Because ATR blocked this effect, cholinergic mechanisms are probably involved in the salicylates' central stimulation of ventilation.
Fleming
H
H
Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Burton
M
M
Johnson
D C
DC
Kazemi
H
H
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D007276:Injections, Intraventricular; D012119:Respiration / Q000187:drug effects* / Q000502:physiology; D012980:Sodium Salicylate / Q000008:administration & dosage / Q000494:pharmacology*; D013990:Tidal Volume / Q000187:drug effects
D001285:Atropine; D012980:Sodium Salicylate