S. Zini et al., AMINOPEPTIDASE-A - DISTRIBUTION IN RAT-BRAIN NUCLEI AND INCREASED ACTIVITY IN SPONTANEOUSLY HYPERTENSIVE RATS, Neuroscience, 78(4), 1997, pp. 1187-1193
Aminopeptidase A is a membrane-bound zinc metalloprotease which cleave
s angiotensin II into angiotensin III. Using a new specific aminopepti
dase A inhibitor, EC33, we evaluated its enzymatic activity in several
microdissected brain nuclei involved in the control of cardiovascular
functions and in the pituitary. We compared this distribution with th
at of the angiotensin I-converting enzyme which converts angiotensin I
to angiotensin II. Aminopeptidase A activity was heterogenously distr
ibuted with a 150-fold difference between the lowest and the highest l
evels. The pituitary and the circumventricular organs were the richest
source of enzyme, followed by the median eminence, the arcuate nucleu
s, the area postrema, the choroid plexus and the supraotic and paraven
tricular nuclei. We did not find any close parallel between aminopepti
dase A and angiotensin I-converting enzyme distributions. We examined
both enzymatic activities in brain nuclei of spontaneously hypertensiv
e rats. Aminopeptidase A activity was higher in the spontaneously hype
rtensive rats than in age-matched Wistar-Kyoto control rats. The diffe
rence was up to 2.5-fold in several brain nuclei involved in the blood
pressure regulation; in contrast, no differences in angiotensin I-con
verting enzyme activity were found in the same regions. The close corr
espondence between the distribution of aminopeptidase A activity and a
ngiotensin receptors and nerve terminals in the brain associated with
the observation that aminopeptidase A activity was overactivated in th
e spontaneously hypertensive rats suggest that this enzyme may contrib
ute, at least in part, to the regulation of cardiovascular functions b
y its ability to convert angiotensin II to angiotensin III. (C) 1997 I
BRO. Published by Elsevier Science Ltd.