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.
Nattie
E E
EE
Department of Physiology, Dartmouth Medical School, Hanover, New Hampshire 03756.
Giddings
B
B
D000136:Acid-Base Equilibrium; D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D001639:Bicarbonates / Q000134:cerebrospinal fluid*; D004047:Diethyl Pyrocarbonate / Q000494:pharmacology*; D005561:Formates / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D006935:Hypercapnia / Q000503:physiopathology*; D011817:Rabbits; D012119:Respiration / Q000187:drug effects*; D014991:Xylazine
D001639:Bicarbonates; D005561:Formates; D014991:Xylazine; D000584:Amiloride; D004047:Diethyl Pyrocarbonate