MOLECULAR CO₂ IS INERT ON CAROTID CHEMORECEPTOR: DEMONSTRATION BY INHIBITION OF CARBONIC ANHYDRASE

¹ Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, Florida

While CO₂ elicits a carotid body response, the simultaneous increase of catalytically formed H₂CO₂ blurs detection of the actual molecular stimulus at the chemoreceptor site. Carbonic anhydrase inhibition creates a delay in CO₂ hydration in vivo and allows a brief exposure of the receptor to the original molecular stimulus, presented as dry gas, without initial alteration of other molecular species unless introduced. Pure CO₂ was injected into the carotid artery of anesthetized dogs in order to elicit ventilatory gasps and brief hyper-ventilation beginning at one to four seconds. Carbonic anhydrase was inhibited by acetazolamide, 20 mg/kg i.v., and the previously effective doses of CO₂ were repeated. Respiratory responses to doses at threshold were eliminated, and responses to higher doses were delayed and diminished. However, prompt ventilatory responses to intracarotid lactic acid (0.15 M) were preserved after acetazolamide. Substitution of saline for blood in perfusion of the carotid system left intact the CO₂ response in normals, as well as the inhibitory effect of acetazolamide. Such findings constitute physiologic evidence for participation of extra vascular enzyme in or near glomus cells. Responses to intracarotid CO₂ injection and inhibition of the prompt effects by acetazolamide indicate that stimulation of carotid chemoreceptor is predominantly through formation of H₂CO₃ or its ions and that molecular CO₂ is inactive.

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