Circulating germinal ACE can substitute for somatic ACE to maintain normal renal structure and fluid homeostasis, but not blood pressure, in Ace -/- mice.
Germinal ACE sufficiency for renal but not BP control in mice warrants caution extrapolating to humans; leaves open compartment-specific ACE targeting in hypertension.
The angiotensin-converting enzyme (ACE) gene encodes two structurally related isozymes, somatic ACE and germinal ACE, that are uniquely expressed in discrete locations in the body. The importance of ACE in these cell types was revealed by generating Ace -/- mice, which exhibit multiple abnormalities including renal structural defects and functions, hypotension, and male sterility. To test the hypothesis that specific physiological functions of ACE are mediated by isozyme-specific and tissue-specific expression patterns, we have used a transgenic approach to develop mouse strains that express just one ACE isoform in the target tissue of Ace -/- mice. The mice described in this report produce germinal ACE in sperm and serum. These mice were as healthy as wild type mice, and the males were fertile. Interestingly, they had normal kidney structure, fluid homeostasis, and partially restored urine concentration despite having low blood pressure. This result demonstrated that circulating germinal ACE is sufficient for maintaining normal kidney structure and fluid homeostasis but insufficient for restoring blood pressure to normal levels.
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Kessler et al. (2002) studied this question.
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