title: Cardiac and renal distribution of ACE and ACE-2 in rats with heart failure.
abstract: Congestive heart failure is often associated with impaired kidney function. Over-activation of the renin-angiotensin-aldosterone system (RAAS) contributes to avid salt and water retention in heart failure. While the expression of angiotensin converting enzyme (ACE), a key enzyme in the synthesis of angiotensin II (Ang II), is well established, the expression of angiotensin converting enzyme-2 (ACE-2), an enzyme responsible for angiotensin 1-7 generation, is largely unknown. This issue is of a special interest since angiotensin 1-7 counteracts many of the proliferative and hypertensive effects of angiotensin II. Therefore, the present study was designed to investigate the expression of both enzymes in the kidney and heart of rats with heart failure. Heart failure (CHF) was induced in male Sprague Dawley rats (n=9) by the creation of a surgical aorto-caval fistula. Sham-operated rats served as controls (n=8). Two weeks after surgery, the animals were sacrificed and their hearts and kidneys were harvested for assessment of cardiac remodeling and ACE and ACE-2 immunoreactivity by immunohistochemical staining. ACE immunostaining was significantly increased in the kidneys (4.34 ± 0.39% vs. 2.96 ± 0.40%, P<0.05) and hearts (4.57 ± 0.54% vs. 2.19 ± 0.37%, P<0.01) of CHF rats as compared with their sham controls. In a similar manner, ACE-2 immunoreactivity was also elevated in the kidneys (4.65 ± 1.17% vs. 1.75 ± 0.29%, P<0.05) and hearts (5.48 ± 1.11% vs. 1.13 ± 0.26%, P<0.01) of CHF rats as compared with their healthy controls. This study showed that both ACE and ACE-2 are overexpressed in the cardiac and renal tissues of animals with heart failure as compared with their sham controls. The increased expression of the beneficial ACE-2 in heart failure may serve as a compensatory response to the over-activity of the deleterious isoform, namely, angiotensin converting enzyme 1(ACE-1).
authors.affiliation: Department of Physiology and Biophysics, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: Ravit
authors.initials: R
authors.lastname: Cohen-Segev
authors.affiliation: Department of Physiology and Biophysics, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: Bahaa
authors.initials: B
authors.lastname: Francis
authors.affiliation: Department of Physiology and Biophysics, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: Niroz
authors.initials: N
authors.lastname: Abu-Saleh
authors.affiliation: Department of Physiology and Biophysics, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: Hoda
authors.initials: H
authors.lastname: Awad
authors.affiliation: Lipid Research Laboratories, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Aviva
authors.initials: A
authors.lastname: Lazarovich
authors.affiliation: Department of Physiology and Biophysics, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: Aviva
authors.initials: A
authors.lastname: Kabala
authors.affiliation: Department of Cardiology, Rambam Medical Center, Haifa, Israel.
authors.forename: Doron
authors.initials: D
authors.lastname: Aronson
authors.affiliation: Department of Physiology and Biophysics, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel; Research Unit, Rambam Medical Center, Haifa, Israel. Electronic address: abassi@tx.technion.ac.il.
authors.forename: Zaid
authors.initials: Z
authors.lastname: Abassi
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D006333:Heart Failure / Q000097:blood / Q000378:metabolism* / Q000652:urine; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2
keywords: Angiotensin 1–7; Angiotensin II; Angiotensin converting enzyme; Angiotensin converting enzyme 2; Heart failure; Kidney; Rat