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 for vascular activity and to study its distribution in the lung. Vascular CA activity was monitored in isolated rat lungs by measuring the rate of CO2 excretion and the magnitude of postcapillary CO2-HCO(3-)-H+ disequilibria. Lungs were perfused with isotonic salines containing gluconate, sulfate, Cl-, or I-, with or without sulfonamide derivatives. Effects of a CA inhibitor purified from porcine blood plasma were also determined. Vascular CA activity was unaffected by gluconate, sulfate, Cl-, and I- (< or = 100 mM). Sulfonamides with vastly different rates of membrane permeation (i.e., readily permeating ethoxzolamide, slowly permeating acetazolamide, and membrane-impermeant quaternary ammonium sulfanilamide) were capable of accessing all vascular CA with similar rates of access. The porcine inhibitor of CA (340 nM) produced a significant, but submaximal, inhibition of vascular CA activity. The data suggest that pulmonary vascular activity reflects a high-activity membrane-bound isozyme, CA IV, which is located on the extracellular luminal surface of capillary endothelial cells.
Heming
T A
TA
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77550.
Vanoye
C G
CG
Stabenau
E K
EK
Roush
E D
ED
Fierke
C A
CA
Bidani
A
A
D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000201:enzymology; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010477:Perfusion; D011652:Pulmonary Circulation / Q000187:drug effects; D011659:Pulmonary Gas Exchange / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology
D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D013449:Sulfonamides; D002256:Carbonic Anhydrases