TY - JOUR
T1 - Effect of hypoxia and hypercapnia on ACE activity in the cerebral microcirculation of anesthetized dogs
AU - Pitt, B. R.
AU - Lister, G.
AU - Dawson, C. A.
AU - Linehan, J. H.
PY - 1986
Y1 - 1986
N2 - 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-phneylalanyl-alanyl-proline ([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 V̄(max) (the maximal rate of cerebral BPAP metabolism) to K(m) (the concentration at V̄(max)/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, V̄(max)/K(m) 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 V̄(max)/K(m)) 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.
AB - 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-phneylalanyl-alanyl-proline ([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 V̄(max) (the maximal rate of cerebral BPAP metabolism) to K(m) (the concentration at V̄(max)/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, V̄(max)/K(m) 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 V̄(max)/K(m)) 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.
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U2 - 10.1152/ajpheart.1986.250.5.h806
DO - 10.1152/ajpheart.1986.250.5.h806
M3 - Article
C2 - 3010743
AN - SCOPUS:0022509038
SN - 0363-6135
VL - 250
SP - H806-H814
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 5 (19/5)
ER -