Differential Expression of Angiotensin-converting Enzyme and Chymase in Dogs with Chronic Mitral Regurgitation

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 important effect on the efficacy of ACE inhibitor treatment in modulating tis...

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Bibliographic Details
Published in:Journal of molecular and cellular cardiology 1999-05, Vol.31 (5), p.1033-1045
Main Authors: Su, Xuefeng, Wei, Chih-Chang, Machida, Naburo, Bishop, Sanford P., Hankes, Gerald H., Dillon, Ray A., Oparil, Suzanne, Dell»Italia, Louis J.
Format: Article
Language:English
Subjects:
Angiotensin II
Angiotensin-converting Enzyme
Animals
Chronic Disease
Chymases
Dogs
Gene Expression Regulation, Enzymologic - physiology
Heart failure
Hypertrophy
Kidney - enzymology
Lung - enzymology
Mitral Valve Insufficiency - metabolism
Myocardium - enzymology
Peptidyl-Dipeptidase A - genetics
Serine Endopeptidases - genetics
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Summary: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 important effect on the efficacy of ACE inhibitor treatment in modulating tissue angiotensin II (ANG II) levels in heart failure. A total of 18 dogs underwent 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 10 mg PO BID. Seventeen dogs underwent a sham-operation: six of these dogs were treated with ramipril for 3 months (10 mg PO BID) and 11 were untreated and followed for 3 months prior to sacrifice. In mitral regurgitation dogs, ANG II 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 levels and ACE activities were increased 2-fold in treated and untreated mitral regurgitation dogs compared to shams (P50% and chymase activity was increased in left ventricle (LV) of mitral regurgitation dogs (P
ISSN:0022-2828
1095-8584
DOI:10.1006/jmcc.1999.0933