INHIBITOR SENSITIVITY OF PULMONARY VASCULAR CARBONIC-ANHYDRASE

The inhibitor sensitivity of pulmonary vascular carbonic anhydrase (CA ) was examined in situ to identify the specific isozyme responsible fo r vascular activity and to study its distribution in the lung. Vascula r CA activity was monitored in isolated rat lungs by measuring the rat e of CO2 excretion and the magnitude of postcapillary CO2-HCO3--H+ dis equilibria. Lungs were perfused with isotonic salines containing gluco nate, sulfate, Cl-, or I-, with or without sulfonamide derivatives. Ef fects of a CA inhibitor purified from porcine blood plasma were also d etermined. Vascular CA activity was unaffected by gluconate, sulfate, Cl-, and I-(less-than-or-equal-to 100 mM). Sulfonamides with vastly di fferent rates of membrane permeation (i.e., readily permeating ethoxzo lamide, slowly permeating acetazolamide, and membrane-impermeant quate rnary ammonium sulfanilamide) were capable of accessing all vascular C A with similar rates of access. The porcine inhibitor of CA (340 nM) p roduced a significant, but submaximal, inhibition of vascular CA activ ity. The data suggest that pulmonary vascular activity reflects a high -activity membrane-bound isozyme, CA IV, which is located on the extra cellular luminal surface of capillary endothelial cells.