Acetazolamide reduces hypoxic pulmonary vasoconstriction in isolated perfused rabbit lungs

Carbonic anhydrase (CA) may modulate regional blood flow by mediating chang es in extra- and intracellular pH. We hypothesized that CA inhibition with acetazolamide would inhibit the kinetics and magnitude of hypoxic pulmonary vasoconstriction (HPV). Isolated rabbit lungs were ventilated and perfused in situ at constant flow, with buffer containing red blood cells. Preparat ions were sequentially challenged with hypoxic (FIO2 0.05) and/or hypercapn ic (FICO2 0.10) gas mixtures for 5 or 10 min. In the experimental groups, a cetazolamide (33 mu M) was added to the perfusate after establishing baseli ne responses, and gas challenges were repeated; control groups were studied without acetazolamide. Acetazolamide reduced the increase in pulmonary art ery pressure (Delta PAP) and the rate of pressure rise by approximately 30- 50% during hypoxia and combined hypoxia/hypercapnia. The reduction in Delta PAP occurred for both 5 and 10 min challenges. Acetazolamide did not affec t expired nitric oxide concentrations. We conclude that acetazolamide reduc es both the magnitude and kinetics of HPV by a mechanism that does not invo lve nitric oxide. (C) 2000 Elsevier Science B.V. All rights reserved.