Effects of alveolar pressure on lung angiotensin-converting enzyme function in vivo.
Angiotensin-converting enzyme lines the luminal surface of pulmonary capillary endothelial cells. The metabolism of its synthetic substrate, 3H-benzoyl-L-phenylalanyl-L-alanyl-L-proline ([3H]BPAP) has been used as an indicator of pulmonary microvascular function. Because the flow-volume status of the pulmonary capillaries is dependent on intra-alveolar pressure, we have studied the effects of airway pressure on endothelial plasmalemmal angiotensin-converting enzyme function in rabbit lungs in vivo. Static inflation of the lungs to a pressure of 0 or 5 Torr did not change percent transpulmonary metabolism and Amax/Km ratio (defined as E X Kcat/Km and thus, under normal conditions, an indirect measure of perfused endothelial luminal surface area) compared with control measurements during conventional mechanical ventilation. When the inflation pressure was increased to 10 Torr, percent metabolism of [3H]BPAP remained unaltered but Amax/Km decreased to 60% of the control value. This decrease was in close relation to the decrease in pulmonary blood flow. Addition of 5 cmH2O positive end-expiratory pressure (PEEP) to the mechanical ventilation also decreased Amax/Km values and pulmonary blood flow but did not influence percent metabolism of [3H]BPAP. These results suggest that the detected alterations in apparent enzyme kinetics were more likely due to hemodynamic changes than to alterations in angiotensin-converting enzyme function. Thus high static alveolar pressures as well as PEEP probably reduced the fraction of perfused microvessels as reflected in changes in Amax/Km ratios. This information should prove useful in interpreting the response of pulmonary endothelial enzymes to injury.
D000818:Animals; D002196:Capillaries / Q000201:enzymology; D004727:Endothelium / Q000201:enzymology; D007700:Kinetics; D008168:Lung / Q000098:blood supply / Q000201:enzymology*; D008297:Male; D009842:Oligopeptides; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011175:Positive-Pressure Respiration; D011312:Pressure; D011650:Pulmonary Alveoli / Q000502:physiology; D011817:Rabbits
D009842:Oligopeptides; C029689:benzoylphenylalanyl-alanyl-proline; D007703:Peptidyl-Dipeptidase A