Maintenance of Normal Blood Pressure and Renal Functions Are Independent Effects of Angiotensin-converting Enzyme

• Published in: The Journal of biological chemistry Vol. 278; no. 23; pp. 21105 - 21112
• Main Authors: Kessler, Sean P., deS. Senanayake, Preenie, Scheidemantel, Thomas S., Gomos, Janette B., Rowe, Theresa M., Sen, Ganes C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.06.2003
• Subjects: Angiotensin I - blood; Angiotensin II - blood; Animals; Blood Pressure - physiology; Endothelium, Vascular - enzymology; Female; Gene Expression Regulation, Enzymologic; Infertility, Male - physiopathology; Kidney Diseases - physiopathology; Kidney Tubules, Proximal - enzymology; Male; Mice; Mice, Inbred Strains; Mice, Knockout; Peptidyl-Dipeptidase A - genetics; Peptidyl-Dipeptidase A - metabolism; Pregnancy; Transgenes - physiology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M302347200

Angiotensin-converting enzyme (ACE) is expressed in many tissues, including vasculature and renal proximal tubules, and its genetic ablation in mice causes abnormal renal structure and functions, hypotension, and male sterility. To test the hypothesis that specific physiological functions of ACE are mediated by its expression in specific tissues, we generated different mouse strains, each expressing ACE in only one tissue. Here, we report the properties of two such strains of mice that express ACE either in vascular endothelial cells or in renal proximal tubules. Because of the natural cleavage secretion process, both groups also have ACE in the serum. Both groups were as healthy as wild-type mice, having normal kidney structure and fluid homeostasis, though males remained sterile, because they lack ACE expression in sperm. Despite equivalent serum ACE and angiotensin II levels and renal functions, only the group that expressed ACE in vascular endothelial cells had normal blood pressure. Expression of ACE, either in renal proximal tubules or in vasculature, is sufficient for maintaining normal kidney functions. However, for maintaining blood pressure, ACE must be expressed in vascular endothelial cells. These results also demonstrate that ACE-mediated blood pressure maintenance can be dissociated from its role in maintaining renal structure and functions.