Renin Inhibition Improves Cardiac Function and Remodeling After Myocardial Infarction Independent of Blood Pressure
Abstract
Methods
Animals and Experimental Protocol
Histological Assessment of Apoptosis by TUNEL Staining
Real-Time RT-PCR
Immunohistological Measurements
Western Blot
Zymography of MMP-9 Activity
Statistical Analysis
Results
Blood Pressure
Parameters Studied | CO | CO Aliskiren 10 mg | CO Aliskiren 50 mg | CO Alsikiren 100 mg |
---|---|---|---|---|
Data are means±SEMs. Data are the results of the pilot study undertaken to obtain a non–blood pressure-lowering dose of aliskiren. It was only treatment with 100 mg/kg of body weight that significantly lowered systolic and diastolic blood pressures. | ||||
*P<0.05 vs CO. | ||||
Systolic blood pressure, mm Hg | 109±6 | 105±4 | 107±4 | 88±5* |
Diastolic blood pressure, mm Hg | 75±4 | 72±5 | 68±5 | 45±7* |
Cardiac Function
Parameters Studied | Sham | Sham Aliskiren | MI | MI Aliskiren |
---|---|---|---|---|
Data are means±SEMs. The heart weight was increased 10 days after MI in the placebo-treated animals, a finding that was attenuated by aliskiren treatment. | ||||
*P<0.05 vs sham. | ||||
†P<0.05 vs MI. | ||||
Body weight, g | 25±2 | 24±1 | 22±2 | 23±3 |
Heart weight, mg | 98±8 | 103±6 | 158±13* | 123±9† |
Myocyte cross-sectional area, μm2 | 148±6 | 152±9 | 196±14* | 174±11† |
Lung weight, wet/dry | 4.2±0.3 | 4.5±0.5 | 6.9±0.9* | 5.3±0.6† |
Parameters Studied | Sham | Sham Aliskiren | MI | MI Aliskiren |
---|---|---|---|---|
Data are means±SEMs. Hemodynamic parameters were measured by conductance catheter 10 days after induction of MI or sham. EF indicates ejection fraction; Ees, end systolic elastance. | ||||
*P<0.05 vs sham placebo. | ||||
†P<0.05 vs MI placebo. | ||||
Systolic blood pressure, mm Hg | 104±4 | 101±3 | 78±6* | 86±5† |
Diastolic blood pressure, mm Hg | 68±3 | 65±4 | 55±4* | 62±4† |
Heart rate, bpm | 456±18 | 445±22 | 475±27 | 489±23 |
Volume end diastolic, μL | 54±3 | 57±2 | 82±4* | 68±5† |
Volume end systolic, μL | 22±3 | 19±3 | 66±5* | 44±3† |
Stroke volume, μL | 30±4 | 33±5 | 16±5* | 23±5† |
Cardiac output, mL/min | 13.6±0.5 | 14.2±0.7 | 7.6±1.1* | 11.1±1.2† |
LV systolic pressure, mm Hg | 106±4 | 104±5 | 78±5* | 89±6† |
dP/dt max, mm Hg/s | 7125±235 | 6987±358 | 4125±458* | 5254±286† |
EF, % | 61±5 | 63±6 | 22±5* | 35±5† |
LV diastolic pressure, mm Hg | 1.1±0.3 | 1.8±0.5 | 12.3±4* | 8.8±4† |
dP/dt min, mm Hg/s | −6254±213 | −6077±268 | −3133±358* | −4125±188† |
Ees, mm Hg/mL | 1.88±0.3 | 1.79±0.4 | 1.13±0.4* | 1.49±0.5† |
Diastolic stiffness, mL−1 | 0.027±0.004 | 0.019±0.006 | 0.130±0.02* | 0.09±0.02† |
Cardiac Apoptosis

Cardiac Hypertrophy

Cardiac Changes in the Extracellular Matrix


Cardiac Renin Levels

Discussion
Perspectives
Acknowledgments
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On the cover: Light micrographs of glomeruli of the kidneys of Sprague-Dawley rats administered saline vehicle (1 mL/h; n=6), angiotensin II (ANGII; 20 ng/kg per minute; n=7), or combined angiotensin II plus l-arginine (L-Arg; 300 µg/kg per minute; n=6) for 9 days. Glomerular sclerosis (blue fibrotic tissue and collapsed capillary structure) is present in the kidneys of rats administered angiotensin II. There is visibly less glomerular injury in rats coadministered l-arginine compared with rats administered angiotensin II alone. (See page 1086.)
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- Cardiac dysfunction after preeclampsia; an overview of pro- and anti-fibrotic circulating effector molecules, Pregnancy Hypertension, 23, (140-154), (2021).https://doi.org/10.1016/j.preghy.2020.12.001
- Cardiovascular Active Peptides of Marine Origin with ACE Inhibitory Activities: Potential Role as Anti-Hypertensive Drugs and in Prevention of SARS-CoV-2 Infection, International Journal of Molecular Sciences, 21, 21, (8364), (2020).https://doi.org/10.3390/ijms21218364
- Aliskiren attenuates cardiac dysfunction by modulation of the mTOR and apoptosis pathways, Brazilian Journal of Medical and Biological Research, 53, 2, (2020).https://doi.org/10.1590/1414-431x20198793
- Normalizing Plasma Renin Activity in Experimental Dilated Cardiomyopathy: Effects on Edema, Cachexia, and Survival, International Journal of Molecular Sciences, 20, 16, (3886), (2019).https://doi.org/10.3390/ijms20163886
- Renin Activity in Heart Failure with Reduced Systolic Function—New Insights, International Journal of Molecular Sciences, 20, 13, (3182), (2019).https://doi.org/10.3390/ijms20133182
- Macrophage Migration Inhibitory Factor (MIF) Expression Increases during Myocardial Infarction and Supports Pro-Inflammatory Signaling in Cardiac Fibroblasts, Biomolecules, 9, 2, (38), (2019).https://doi.org/10.3390/biom9020038
- Role of renin-angiotensin system antagonists in the prevention of bevacizumab- and sunitinib-mediated cardiac dysfunction, American Journal of Physiology-Heart and Circulatory Physiology, 316, 3, (H446-H458), (2019).https://doi.org/10.1152/ajpheart.00344.2018
- Effects of low dose of aliskiren on isoproterenol-induced acute myocardial infarction in rats, Physiology International, 105, 2, (127-144), (2018).https://doi.org/10.1556/2060.105.2018.2.11
- TAK-272 (imarikiren), a novel renin inhibitor, improves cardiac remodeling and mortality in a murine heart failure model, PLOS ONE, 13, 8, (e0202176), (2018).https://doi.org/10.1371/journal.pone.0202176
- Aliskiren Improves Ischemia- and Oxygen Glucose Deprivation-Induced Cardiac Injury through Activation of Autophagy and AMP-Activated Protein Kinase, Frontiers in Pharmacology, 8, (2017).https://doi.org/10.3389/fphar.2017.00819
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