The RAS (renin–angiotensin system) is activated after MI (myocardial infarction), and RAS blockade with ACEis [ACE (angiotensin-converting enzyme) inhibitors] or ARBs (angiotensin receptor blockers) slows but does not completely prevent progression to heart failure. Cardiac ACE is increased after MI and leads to the formation of the vasoconstrictor AngII (angiotensin II). The enzyme ACE2 is also activated after MI and degrades AngII to generate the vasodilator Ang-(1–7) [angiotensin-(1–7)]. Overexpression of ACE2 offers cardioprotective effects in experimental MI, but there is conflicting evidence as to whether the benefits of ACEis and ARBs are mediated through increasing ACE2 after MI. In the present study, we assessed the effect of an ACEi and ARB, alone and in combination, on cardiac ACE2 in a rat MI model. MI rats received vehicle, ACEi (ramipril; 1 mg/kg of body weight), ARB (valsartan; 10 mg/kg of body weight) or combination (ramipril at 1 mg/kg of body weight and valsartan at 10 mg/kg of body weight) orally for 28 days. Sham-operated rats were also studied and received vehicle alone. MI increased LV (left ventricular) mass (P<0.0001), impaired cardiac contractility (P<0.05) and activated cardiac ACE2 with increased gene (P<0.05) and protein expression (viable myocardium, P<0.05; border zone, P<0.001; infarct, P<0.05). Ramipril and valsartan improved remodelling (P<0.05), with no additional effect of dual therapy. Although ramipril inhibited ACE, and valsartan blocked the angiotensin receptor, neither treatment alone nor in combination augmented cardiac ACE2 expression. These results suggest that the cardioprotective effects of ramipril and valsartan are not mediated through up-regulation of cardiac ACE2. Strategies that do augment ACE2 after MI may be a useful addition to standard RAS blockade after MI.
Skip Nav Destination
Article navigation
Research Article|
August 01 2012
Combination renin–angiotensin system blockade and angiotensin-converting enzyme 2 in experimental myocardial infarction: implications for future therapeutic directions
Luke J. Burchill;
Luke J. Burchill
*Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia
†Peter Munk Cardiac Centre, Toronto General Hospital, Toronto, Canada
Search for other works by this author on:
Elena Velkoska;
Elena Velkoska
*Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia
Search for other works by this author on:
Rachael G. Dean;
Rachael G. Dean
*Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia
Search for other works by this author on:
Karen Griggs;
Karen Griggs
*Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia
Search for other works by this author on:
Sheila K. Patel;
Sheila K. Patel
*Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia
Search for other works by this author on:
Louise M. Burrell
*Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia
‡Department of Cardiology, Austin Health, Heidelberg, Victoria, Australia
Correspondence: Professor Louise Burrell (email [email protected]).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
March 30 2012
Revision Received:
June 14 2012
Accepted:
June 20 2012
Accepted Manuscript online:
June 20 2012
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2012 Biochemical Society
2012
Clin Sci (Lond) (2012) 123 (11): 649–658.
Article history
Received:
March 30 2012
Revision Received:
June 14 2012
Accepted:
June 20 2012
Accepted Manuscript online:
June 20 2012
Citation
Luke J. Burchill, Elena Velkoska, Rachael G. Dean, Karen Griggs, Sheila K. Patel, Louise M. Burrell; Combination renin–angiotensin system blockade and angiotensin-converting enzyme 2 in experimental myocardial infarction: implications for future therapeutic directions. Clin Sci (Lond) 1 December 2012; 123 (11): 649–658. doi: https://doi.org/10.1042/CS20120162
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() |