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Regional distribution of angiotensin converting enzyme(ACE) in the rat kidney was studied. The ACE activities in the inner cortex and outer medulla were about 10 and 5 times those in the outer cortex, respectively. The activity in the inner medulla or papilla was much the same as that in the outer cortex. Immunofluorescence was greatest in the proximal tubules in the inner cortex, while the outer medulla and the inner medulla or papilla showed a weak fluorescence. The brush border membranes isolated from the inner cortex also possessed about 10 times the ACE activity seen in the outer cortex. The results indicate that the major source of renal ACE is not the proximal convoluted tubules in the outer cortex, but rather the brush border membranes of proximal tubules in the inner cortex. The contribution of ACE in the inner cortex would therefore be predominant.

With regard to the concept of the local action of the renin angiotensin system (RAS) involved in blood pressure regulation, the presence of angiotensin converting enzyme (ACE) in a variety of organs suggests that locally produced angiotensin II (ANG II) shares, at least to some extent, the actions of this peptide on respective target organs of ANG II. However, renal ACE is less well understood for its relationship between blood pressure and enzyme activity. In our present studies, with a single oral administration of enalapril to spontaneously hypertensive rats, the inhibition of renal cortical and aortic ACE, but not plasma ACE, coincided with a reduction in blood pressure. Development of high blood pressure in stroke-prone, spontaneously hypertensive rats (SHRSP) from 7 to 22 weeks of age was accompanied by an increase in ACE activity in the renal cortex. Aortic and pulmonary ACE also tended to increase with age, but was less prominent. Isolated brush-border membranes contained abundant ACE, both in Wistar-Kyoto rats and SHRSP, and the levels of ACE in renal cortical homogenates closely correlated to the levels of brush-border ACE. Thus, changes in renal cortical ACE activity in response to the ACE inhibition and in cases of SHRSP in relation to aging are apparently associated with changes in blood pressure. It is likely that renal cortical ACE activity reflects the enzyme activity in the brush borders. Thus, brush-border ACE should probably be taken into account when discussing possible roles of renal ACE.