Determinants of CO2 generation and maintenance in the renal cortex: role of metabolic CO2 production and diffusive CO2 transfer.

We have developed a mathematical model utilizing steady-state mass balance considerations in a compartmental analysis of bicarbonate reabsorption in the superficial proximal tubule and associated vasculature in order to describe quantitatively the determinants of the elevated PCO2 in the renal cortex. This analysis demonstrated for the first time that diffusive transfer of CO2 between vascular segments coupled with metabolic CO2 production could account for the PCO2 measured experimentally. In the present study the predictive value of the model was extended by comparing model-predicted and measured values for PCO2 before and after administration of metabolic and transport inhibitors. In control conditions diffusive CO2 transfer (FCO2) in combination with accepted levels of metabolic CO2 production (MCO2) can account for an elevation in PCO2 to 60 mm Hg. During rotenone and DNP administration the model predicts values for PCO2 which approximate closely the value measured in vivo. In addition, the model demonstrates that the reduction in PCO2 after rotenone and increase in PCO2 after DNP can be accounted for by parallel changes in MCO2 alone as expected. In each case a significant contribution from FCO2 is necessary, however. Therefore, this study demonstrates close agreement in both the magnitude and direction of predicted and determined values in cortical PCO2 in a variety of experimental conditions, thus, supporting a dual role for the major determinants: metabolic CO2 production and diffusive vascular to vascular CO2 transfer.