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(Hypertension. 1999;33:740-745.)
© 1999 American Heart Association, Inc.

Scientific Contribution

Kidney Aminopeptidase A and Hypertension, Part I

Spontaneously Hypertensive Rats

Dennis P. Healy; Lijun Song

From the Department of Pharmacology, Mount Sinai School of Medicine of the City University of New York, New York, NY.

Correspondence to Dr Dennis P. Healy, Department of Pharmacology, Box 1215, Mount Sinai School of Medicine, One Gustave L. Levy Pl, New York, NY 10029. E-mail d_healy{at}smtplink.mssm.edu

Abstract—Tissue and plasma levels of aminopeptidase A (APA), the principal enzyme that hydrolyzes angiotensin II (Ang II) to angiotensin III, were measured in spontaneously hypertensive rats (SHR) and their normotensive control strain at 3 different ages corresponding to prehypertensive (4 weeks), developing (8 weeks), and established (16 weeks) phases of hypertension. Plasma APA activity was significantly but modestly elevated in SHR at all 3 ages compared with normotensive Wistar-Kyoto rats. Likewise, levels of APA in brain, heart, and adrenal gland were generally, but again only moderately, elevated in SHR at all ages. However, a large increase in APA activity was seen within the kidney in which APA levels were elevated 41%, 51%, and 68% in SHR at 4, 8, and 16 weeks of age, respectively. Kidney APA levels were also significantly increased in immunoblots from 8- and 16-week-old SHR. Glomeruli isolated from 16-week-old SHR had 57% higher APA activity and increased immunoreactivity compared with Wistar-Kyoto rats. To determine whether the increase in kidney APA activity in SHR was related to Ang II levels, SHR were treated for 2 weeks with the angiotensin-converting enzyme inhibitor captopril. Captopril treatment reduced blood pressure to normotensive values and resulted in a 25% reduction in kidney APA activity. These results suggest that APA expression in the kidney may be regulated by activity of the renin-angiotensin system. If so, this would further suggest that upregulation of APA during conditions in which Ang II levels were elevated would have a protective effect against Ang II–mediated cardiovascular diseases, whereas a decrease in APA expression or a failure to upregulate would exacerbate such conditions.

Key Words: aminopeptidases • angiotensin II • angiotensin III • hypertension • kidney • kidney glomerulus

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