AJP - Heart and Circulatory Physiology, Vol 250, Issue 5 806-H814, Copyright © 1986 by American Physiological Society
Effect of hypoxia and hypercapnia on ACE activity in the cerebral microcirculation of anesthetized dogs
B. R. Pitt, G. Lister, C. A. Dawson and J. H. Linehan
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.
