Acetazolamide reduces hypoxic pulmonary vasoconstriction in isolated perfused rabbit lungs

Carbonic anhydrase (CA) may modulate regional blood flow by mediating changes 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. Preparations were sequentially challenged with hypoxic (FI(O(2)) 0.05) and/or hypercapnic (FI(CO(2)) 0.10) gas mixtures for 5 or 10 min. In the experimental groups, acetazolamide (33 microM) was added to the perfusate after establishing baseline responses, and gas challenges were repeated; control groups were studied without acetazolamide. Acetazolamide reduced the increase in pulmonary artery pressure (DeltaPAP) and the rate of pressure rise by approximately 30-50% during hypoxia and combined hypoxia/hypercapnia. The reduction in DeltaPAP occurred for both 5 and 10 min challenges. Acetazolamide did not affect expired nitric oxide concentrations. We conclude that acetazolamide reduces both the magnitude and kinetics of HPV by a mechanism that does not involve nitric oxide.