The transport of carbon dioxide from the tissues to the lungs is significantly enhanced by the presence of the enzyme, carbonic anhydrase, within red cells. This enzyme accelerates the conversion of CO2 to HCO3- in the tissues and the subsequent release of CO2 from HCO3- in the lungs. Evidence has recently been obtained that carbonic anhydrase is also located on the inner surface of endothelial cells of the lung and leg, at a site which is more accessible to plasma HCO3- than the enzyme within the red cells. It is the object of this project to confirm preliminary observations that there is insufficient carbonic anhydrase in the renal circulation to ensure CO2-HCO3- equiplibration. This deficiency may help explain high PCO2 tensions which have been found in the cortical vessels of the kidney. We also intend to test the hypothesis that the endothelial carbonic anhydrase of the lung and leg is present on the outer surfaces of these cells by using inhibitors which are linked to large dextran molecules. These same agents will be used to determine the relative roles of red cell and vascular carbonic anhydrase upon CO2 transport by selectively blocking the extracellular enzyme sites. Additional studies will be performed in which bicarbonate transport across red cell membranes is inhibited with agents which block HCO3- exchange. An effort will also be made to detect carbonic anhydrase activity in the splenic and hepatic circulations. We believe that these studies will provide a better understanding of situations in which CO2 is retained (primarily lung disorders) as well as the manner in which CO2 tensions influence acid secretion by the kidney.
| Dodek, P M; Minshall, D K; Edwards Jr, J E et al. (1990) A new stimulation of the interaction between neutrophils and pulmonary endothelial cells. Microvasc Res 39:105-119 |
| Lipsen, B; Effros, R M (1988) CO2 and bicarbonate exchange in the rat liver. J Appl Physiol 65:2736-43 |
| Effros, R M; Taki, K; Dodek, P et al. (1988) Exchange of labeled bicarbonate and carbon dioxide with erythrocytes suspended in an elutriator. J Appl Physiol 64:569-76 |
| Roston, W L; Whipp, B J; Davis, J A et al. (1987) Oxygen uptake kinetics and lactate concentration during exercise in humans. Am Rev Respir Dis 135:1080-4 |
| Effros, R M (1985) Lung water measurements with the mean transit time approach. J Appl Physiol 59:673-83 |
