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Effects of ACE Inhibitor, AT1 Antagonist, and Combined Treatment in Mice with Heart Failure
- Source :
- Journal of Cardiovascular Pharmacology. 36:472-480
- Publication Year :
- 2000
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2000.
-
Abstract
- We tested the hypothesis that a combination of angiotensin-converting enzyme inhibitor (ACEi) and angiotensin II type 1 receptor antagonist (AT1-ant) may have an additive cardioprotective effect in mice with heart failure (HF), because these two agents could have other mechanisms of action besides interrupting the renin-angiotensin system. ACEi prevent degradation of bradykinin. During treatment with AT1-ant, increased angiotensin II could activate AT2 receptors, with an antitrophic effect. To test this hypothesis, we used a mouse model of HF induced by myocardial infarction. Seven days after surgery, mice were divided into six groups and treated for 23 weeks: (a) sham ligation; (b) HF-vehicle; (c) HF-ACEi; (d) HF-AT1-ant; (e) HF-ACEi + AT1-ant (half dose of each); and (f) HF-ACEi + AT1-ant (full dose of each). Cardiac function was evaluated in conscious mice during the treatment period. The HF-vehicle group showed significantly decreased left ventricular (LV) ejection fraction (EF), shortening fraction (SF), and cardiac output (CO) and increased LV dimensions, interstitial collagen, and myocyte cross-sectional area (MCSA) compared with controls. Treatment with ACEi or AT1-ant significantly increased EF, SF, and CO and decreased LV dimensions and MCSA in mice with HF. However, a combination of these drugs did not improve cardiac function more than ACEi or AT1-ant alone. We concluded that ACEi and AT1-ant have similar cardioprotective effects and may reach maximal effect when given individually; thus no further improvement can be achieved with combined therapy in mice with HF.
- Subjects :
- Male
Cardiac function curve
Ramipril
medicine.medical_specialty
Myocardial Infarction
Tetrazoles
Angiotensin-Converting Enzyme Inhibitors
Mice
Internal medicine
medicine
Animals
cardiovascular diseases
Cardiac Output
Ventricular remodeling
Antihypertensive Agents
Heart Failure
Pharmacology
Angiotensin II receptor type 1
Ejection fraction
Ventricular Remodeling
business.industry
Angiotensin II
Myocardium
Imidazoles
Heart
Stroke Volume
Organ Size
medicine.disease
Mice, Inbred C57BL
Endocrinology
Echocardiography
Heart failure
Chronic Disease
ACE inhibitor
cardiovascular system
Female
Angiotensin I
Cardiology and Cardiovascular Medicine
business
medicine.drug
Subjects
Details
- ISSN :
- 01602446
- Volume :
- 36
- Database :
- OpenAIRE
- Journal :
- Journal of Cardiovascular Pharmacology
- Accession number :
- edsair.doi.dedup.....b9165680c7b9df3d9ce007a52535b1dd