Acetazolamide does not alter hypercapnia‐induced changes in phrenic burst amplitude and frequency in arterially‐perfused adult rat

Abstract

In adult mammals, inhibition of carbonic anhydrase (CA) has been shown to elicit a powerful stimulation of respiratory amplitude (depth) and frequency in a manner similar to that observed in response to hypercapnia. Although CA has been proposed to participate in central CO2 chemoreception, different effects on central chemosensitivity have been suggested based on studies from adult in vivo versus neonatal in vitro preparations. The current study was therefore undertaken to evaluate the role of CA on CO2-chemosensitivity in an arterially-perfused adult rat preparation (n=7). To address this issue, we recorded phrenic nerve discharge in response to increasing CO2 from 5% to 10% before and during blockade of CA with acetazolamide (AZ, 167–333 nM) or methazolamide (MZ; 167 nM). Before AZ/MZ, hypercapnia increased phrenic burst frequency and amplitude by ~41% (P<0.05) and ~25% (P=0.1), respectively; the frequency increase was mediated by a marked reduction in TI (~24%; P<0.02) and a small decrease in TE (~15%; P=0.2). During AZ/MZ perfusion, hypercapnia increased phrenic burst frequency and amplitude, and the magnitude of these increases was similar to those observed without AZ/MZ (freq, P=0.96; amp, P=0.22); similar reductions in TI and TE were also noted (without vs with, P=0.46 and P=0.98, respectively). In addition, the onset latency of the CO2 response was not altered by AZ/MZ perfusion. These findings suggest that CA is not involved in CO2 chemoreception in the arterially-perfused adult rat preparation. Supported by NS045321