Effects of dextran-bound inhibitors on carbonic anhydrase activity in isolated rat lungs.
Effects of macromolecular Prontosil-dextran inhibitors (PD) on carbonic anhydrase (CA) activity in isolated rat lungs were studied. Isolated lungs were perfused with Krebs-Ringer bicarbonate (KRB) solutions containing no inhibitor, PD 100,000 (mol wt 100,000), PD 5,000 (mol wt 5,000), or low-molecular-weight inhibitors (Prontosil or acetazolamide). The time course of effluent perfusate pH equilibration was measured in a stop-flow pH electrode apparatus. Pulmonary CO2 excretion (Vco2) was monitored by continuously recording expired CO2 concentration. The lungs were ventilated with room air and perfused at 37 degrees C with KRB prebubbled with 5% CO2- 20% O2- 75% N2. The results obtained show that both the low-molecular-weight inhibitors and PD's caused postcapillary pH disequilibria (delta pH) in effluent perfusate. However, only acetazolamide and Prontosil caused a reduction in Vco2. These results suggest that there is an intravascular CA, presumably associated with endothelial cell membranes, that is accessible to all inhibitors used and is responsible in part for equilibration of the CO2- HCO3- -H+ reactions in the perfusate but, under the conditions used, does not affect CO2 excretion; and there is an extravascular (possibly intracellular) CA that can be inhibited by low-molecular-weight inhibitors, is primarily responsible for enhanced CO2 transfer across the alveolar-capillary barrier (perhaps via facilitation of CO2 diffusion), and is in part responsible for pH equilibration.
D000086:Acetazolamide / Q000494:pharmacology; D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology*; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D003911:Dextrans / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D008168:Lung / Q000201:enzymology*; D008297:Male; D008970:Molecular Weight; D010477:Perfusion; D011659:Pulmonary Gas Exchange; D051381:Rats; D011919:Rats, Inbred Strains; D010128:p-Aminoazobenzene / Q000031:analogs & derivatives / Q000494:pharmacology*; D044482:Benzeneacetamides
D000086:Acetazolamide; D001391:Azo Compounds; D002257:Carbonic Anhydrase Inhibitors; D003911:Dextrans; D010128:p-Aminoazobenzene; C003359:sulfamidochrysoidine; D044482:Benzeneacetamides