Effects of amiloride and diethyl pyrocarbonate on CSF HCO-3 and ventilation in hypercapnia

Amiloride (10(-3) M), a Na+-H+ countertransport inhibitor, infused into the cisterna magna (10 microliter/min for 40 min) of ketamine-xylazine-anesthetized rabbits decreased the cerebrospinal fluid (CSF) HCO3- response to 3 h of hypercapnia [arterial PCO2 (PaCO2) = 60 Torr] by 21.6% (mean delta CSF [HCO3-]/delta PaCO2 0.232 vs. 0.296 mmol.l-1.Torr-1, P less than 0.05). Diethyl pyrocarbonate (DEPC, 10(-3) M), a histidine-blocking agent, infused into the cisterna magna decreased the CSF HCO3- response to hypercapnia by 25.3% (mean delta CSF [HCO3-]/delta PaCO2, 0.230 vs. 0.308 mmol.l-1.Torr-1, P less than 0.02). DEPC is known to inhibit the ventilatory response to hypercapnia (E. Nattie. Respir. Physiol. 64: 161-176, 1986) by a direct effect at the ventrolateral medulla (E. Nattie. J. Appl. Physiol. 61: 843-850, 1986). In this study amiloride had no significant effect on the ventilatory response to hypercapnia. The interpretation is that a Na+-H+ countertransport protein, perhaps with a histidine at a key location, is involved in CSF acid-base regulation and that amiloride appears to have no effects on the chemoreception process. DEPC appears to have effects on chemoreception and on CSF acid-base regulation.