Xf. Su et al., Differential expression of angiotensin-converting enzyme and chymase in dogs with chronic mitral regurgitation, J MOL CEL C, 31(5), 1999, pp. 1033-1045
The current study tested the hypothesis that angiotensin-converting enzyme
(ACE) and chymase expression are subject to different regulatory processes
in the heart, as well as the lungs and kidneys and, as a result, have an im
portant effect on the efficacy of ACE inhibitor treatment in modulating tis
sue angiotensin II (ANG II) levels in heart failure. A total of 18 dogs und
erwent the induction of mitral regurgitation and were followed for 5 months
, Eleven dogs were untreated and seven received the ACE-inhibitor ramipril
at a dose of 10mg PO BID. Seventeen dogs underwent a sham-operation: six of
these dogs were treated with ramipril for 3 months (10mg PO BID) and 11 we
re untreated and followed for 3 months prior to sacrifice. In mitral regurg
itation dogs, ANG LI levels were increased >2-fold in left ventricle, lungs
, and kidney! but were normalized with ACE inhibitor-treatment only in the
left ventricle. In the left ventricle and lungs steady state ACE mRNA level
s and ACE activities were increased 2-fold in treated and untreated mitral
regurgitation dogs compared to shams (P<0.05, ANOVA). In contrast, chymase
mRNA levels were decreased by >50% and chymase activity was increased in le
ft ventricle (LV) of mitral regurgitation dogs (P<0.05), Neither chymase mR
NA nor chymase activity could be detected in the kidney; however, kidney AC
E mRNA and ACE activity were significantly upregulated in treated and untre
ated mitral regurgitation dogs (P<0.05). These results suggest that ACE and
chymase expression are regulated differentially in the dog in response to
chronic mitral regurgitation and ACE inhibitor treatment. Further, these re
sponses, as well as regulation of ANG II formation, are organ specific. (C)
1999 Academic Press.