Delayed ventilatory response to CO2 after carbonic anhydrase inhibition with acetazolamide administration in the anesthetized rat.
In order to estimate to what extent the stimulatory action of CO2 on ventilation is mediated by the formation of H+, we studied effects on the temporal profile of ventilatory response to CO2 of carbonic anhydrase (CA) inhibition with acetazolamide in the halothane anesthetized spontaneously breathing rat. Since hydration reaction of CO2 yielding H+ is delayed by CA inhibition, the time courses of changes in tidal volume (VT), respiratory frequency (f), and minute ventilation (VE) in response to a stepwise increase in end-tidal PCO2 (delta PETCO2 15 mmHg) were compared before (control state) and after i.v. injection of acetazolamide (50 mg/kg) in the hyperoxic condition. In the control state, an increase in VT was significantly slower than that in f, and the mean response half-times (T1/2) for the increase in VT, f, and VE were 50.6, 18.1, and 31.0 s, respectively. After acetazolamide administration, responses to CO2, especially f-response and consequently VE-response became much slower, and the T1/2 for VT, f, and VE were 67.9, 55.0, and 63.0 s, respectively. The delay in VT-response was not statistically significant. The magnitude of increase in VE in the steady state hypercapnic stimulation was almost the same before and after acetazolamide administration. The results suggest that a rapid increase in f during CO2 inhalation occurs predominantly through an increase in H+ produced by hydration of CO2 with CA, whereas VT-response may occur without involvement of this process. The different time courses of VT- and f-responses and possible effects of molecular CO2 and/or H+ on the regulatory mechanisms for ventilatory pattern were discussed.
Tojima
H
H
Department of Chest Medicine, School of Medicine, Chiba University, Japan.
Kuriyama
T
T
Fukuda
Y
Y
D000086:Acetazolamide / Q000008:administration & dosage / Q000494:pharmacology*; D000769:Anesthesia, Inhalation / Q000379:methods; D000818:Animals; D002245:Carbon Dioxide / Q000494:pharmacology*; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D006935:Hypercapnia / Q000503:physiopathology; D007275:Injections, Intravenous; D008297:Male; D011522:Protons; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration / Q000187:drug effects*; D013997:Time Factors
D002257:Carbonic Anhydrase Inhibitors; D011522:Protons; D002245:Carbon Dioxide; D000086:Acetazolamide