AMINOPEPTIDASE-A - DISTRIBUTION IN RAT-BRAIN NUCLEI AND INCREASED ACTIVITY IN SPONTANEOUSLY HYPERTENSIVE RATS

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.