Carbonic anhydrase and control of breathing: different effects of benzolamide and methazolamide in the anaesthetized cat.
1. The effect of inhibition of erythrocyte carbonic anhydrase on the ventilatory response to CO2 was studied by administering benzolamide (70 mg kg-1, i.v.), an inhibitor which does not cross the blood-brain barrier, to carotid body denervated cats which were anaesthetized with chloralose-urethane. 2. In the same animals the effect on the ventilatory response to CO2 of subsequent inhibition of central nervous system (CNS) carbonic anhydrase was studied by infusing methazolamide (20 mg kg-1), an inhibitor which rapidly penetrates into brain tissue. 3. The results show that inhibition of erythrocyte carbonic anhydrase by benzolamide leads to a decrease in the slope of the normoxic CO2 response curve, and a decrease of the extrapolated arterial PCO2 at zero ventilation. 4. Inhibition of CNS carbonic anhydrase by methazolamide results in an increase in slope and alpha-intercept of the ventilatory CO2 response curve. 5. Using a mass balance equation for CO2 of a brain compartment, it is argued that inhibition of erythrocyte carbonic anhydrase results in a decrease in slope of the in vivo CO2 dissociation curve, which can explain the effects of benzolamide. 6. The changes in slope and intercept induced by methazolamide are discussed in relation to effects on neurones containing carbonic anhydrase, which may include central chemoreceptors.
Teppema
L
L
Department of Physiology, University of Leiden, The Netherlands.
Berkenbosch
A
A
DeGoede
J
J
Olievier
C
C
D000138:Acidosis / Q000503:physiopathology; D000758:Anesthesia; D000818:Animals; D001574:Benzolamide / Q000494:pharmacology*; D001639:Bicarbonates / Q000097:blood; D002245:Carbon Dioxide / Q000097:blood; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D002344:Carotid Body / Q000502:physiology; D002346:Carotid Sinus / Q000294:innervation; D002415:Cats; D004912:Erythrocytes / Q000201:enzymology; D007275:Injections, Intravenous; D008704:Methazolamide / Q000494:pharmacology*; D012119:Respiration / Q000187:drug effects / Q000502:physiology*
D001639:Bicarbonates; D002257:Carbonic Anhydrase Inhibitors; D002245:Carbon Dioxide; D002256:Carbonic Anhydrases; D001574:Benzolamide; D008704:Methazolamide