Effect of hypoxia and hypercapnia on ACE activity in the cerebral microcirculation of anesthetized dogs.
Angiotensin-converting enzyme (ACE) activity of the cerebral microcirculation of anesthetized dogs was measured from cerebral venous outflow curves after bolus injection of a synthetic ACE substrate, [3H]benzoyl-phenylalanyl-alanylproline ([3H]BPAP), into a common carotid artery. Cerebral BPAP metabolism was quantified by measuring the concentration of [3H]benzoyl-phenylalanine (the product of BPAP hydrolysis by ACE) in blood samples from the sagittal sinus after occlusion of the lateral sinuses with bone wax. Instantaneous BPAP metabolism in each sample increased as a function of time after injection, suggestive of perfusion heterogeneity, and averaged 59 +/- 4% (n = 8) over a single pass during normoxia and normocapnia. The ratio of Vmax (the maximal rate of cerebral BPAP metabolism) to Km (the concentration at Vmax/2), was calculated from instantaneous outflow curves using a model based on first-order kinetics. Increases in cerebral blood flow during either hypoxia or hypercapnia significantly reduced BPAP metabolism to 33 +/- 3 (n = 7) and 24 +/- 3% (n = 5), respectively; however, Vmax/Km of ACE activity (0.19 +/- 0.03 ml/s) was not affected by either condition. The lack of change in apparent kinetics of ACE activity (i.e., in Vmax/Km) during hypoxia or hypercapnia suggests that recruitment of cerebral capillaries was not a quantitatively significant factor in controlling BPAP metabolism with this degree of either hypoxia or hypercapnia.
D000758:Anesthesia; D000818:Animals; D002560:Cerebrovascular Circulation; D004285:Dogs; D006935:Hypercapnia / Q000201:enzymology*; D000860:Hypoxia / Q000201:enzymology*; D007201:Indicator Dilution Techniques; D007700:Kinetics; D008433:Mathematics; D008833:Microcirculation; D009842:Oligopeptides / Q000097:blood; D007703:Peptidyl-Dipeptidase A / Q000097:blood*; D014316:Tritium
D009842:Oligopeptides; D014316:Tritium; C029689:benzoylphenylalanyl-alanyl-proline; D007703:Peptidyl-Dipeptidase A