Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/11524
Title: Combination renin-angiotensin system blockade and angiotensin-converting enzyme 2 in experimental myocardial infarction: implications for future therapeutic directions.
Authors: Burchill, Luke J;Velkoska, Elena;Dean, Rachael G;Griggs, Karen;Patel, Sheila K;Burrell, Louise M
Affiliation: Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Issue Date: 1-Dec-2012
Citation: Clinical Science (london, England : 1979); 123(11): 649-58
Abstract: 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.
Internal ID Number: 22715807
URI: http://ahro.austin.org.au/austinjspui/handle/1/11524
DOI: 10.1042/CS20120162
URL: http://www.ncbi.nlm.nih.gov/pubmed/22715807
Type: Journal Article
Subjects: Angiotensin II Type 1 Receptor Blockers.pharmacology.therapeutic use
Angiotensin-Converting Enzyme Inhibitors.pharmacology.therapeutic use
Angiotensins.blood
Animals
Drug Therapy, Combination
Female
Gene Expression Regulation, Enzymologic.drug effects
Heart.drug effects.physiopathology
Hemodynamics.drug effects
Immunohistochemistry
Myocardial Infarction.drug therapy.genetics.metabolism
Myocardium.metabolism.pathology
Organ Size.drug effects
Peptidyl-Dipeptidase A.blood.genetics.metabolism
Ramipril.pharmacology.therapeutic use
Rats
Rats, Sprague-Dawley
Renin.blood
Renin-Angiotensin System.drug effects
Reverse Transcriptase Polymerase Chain Reaction
Tetrazoles.pharmacology.therapeutic use
Valine.analogs & derivatives.pharmacology.therapeutic use
Appears in Collections:Journal articles

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