In humans, the insertion/deletion polymorphism in the angiotensin converting enzyme (
ACE) gene accounts for half of the variance in plasma ACE activity. The deletion allele is associated with high plasma ACE activity,
cardiovascular disease, and renal disease. In rat, a similar association is found between the B and L alleles of a microsatellite
marker in the
ACE gene. We identified the B/L variation in the Wistar outbred rat and bred two lines homozygous for the two alleles (WU-B and
WU-L). ACE activity was measured in serum, heart, kidney, and aorta homogenates. Immunohistochemistry and
ACE mRNA expression were performed in heart, kidney, and aortic tissue. Aortic rings were collected and stimulated with AngI,
AngII, and AngI with Lisinopril to measure ACE functional activity by vasoconstrictor response. Serum, heart, and kidney ACE
activity and kidney mRNA expression were two-fold higher in WU-B. Kidney staining showed a clear difference in tubular
ACE expression, with more staining in WU-B. While in aorta ACE activity and mRNA expression was twofold higher in WU-L, functional
conversion of AngI was higher in WU-B, indicating either a functional difference in AngI to AngII conversion between the two
alleles due to different splicing or the presence of other factors involved in the conversion that are differentially expressed
as the result of differences in the
ACE alleles. The newly developed WU-B and WU-L lines show tissue-specific differences in ACE expression and activity. This provides
an experimental tool to study the pathophysiologic consequences of differences in
ACE alleles in renal and cardiovascular disease.
J. Kamilic and A. T. Lely contributed equally to this work.