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A Model of Cardiac Remodeling Through Constriction of the Abdominal Aorta in Rats
Published on: December 2, 2016
Regression of cardiac hypertrophy in cyp1a1ren-2 transgenic rats
Barbara S Peters1, Rami Dornaika, Norbert Hosten
1Department of Cardiovascular Medicine, Institute of Physiology, University of Greifswald, Karlsburg, Germany. bspeters@gmx.de
Purpose:
To evaluate the usefulness of the cyp1a1ren-2 transgenic rat model of inducible hypertension for studies of the development and regression of cardiac hypertrophy.
Materials And Methods:
Cyp1a1ren-2 rats received a diet containing 0% or 0.167% indole-3-carbinonl (I3C) for 4 weeks to induce hypertension. Cardiac magnetic resonance imaging (MRI) at 7 T was performed every second week for 10 weeks to measure left ventricular mass and the ejection fraction. Concomitantly, in six cyp1a1ren-2 rats blood pressure was recorded telemetrically.
Results:
Plasma prorenin concentrations rose from 138 ± 38 to 15,490 ± 3990 ng/angiotensin I/mL/h (P < 0.001) in I3C-treated transgenic rats and returned to basal levels after cessation of I3C. Mean blood pressure increased to a plateau of 169 ± 11 mmHg by the second week of induction. After cessation of I3C (day 28), arterial pressure dropped to values slightly below those prior to induction within 4 days (basal: 106 ± 7 mmHg, day 32: 103 ± 21 mmHg; NS). At day 28, left ventricular mass was increased by 39% vs. 4% in controls (P < 0.001) without changes of the ejection fraction. Cardiac hypertrophy was completely reversed at day 70, as evaluated by MRI.
Conclusion:
The cyp1a1ren-2 transgenic rat is a useful model to study reversal and healing in the absence of surgical interventions.
Insights
The cyp1a1ren-2 transgenic rat model effectively induces and reverses cardiac hypertrophy. This model is valuable for studying hypertension-related cardiac remodeling and its resolution.
Area of Science:
- Cardiovascular Research
- Translational Medicine
- Animal Models
Background:
- Cardiac hypertrophy is a significant risk factor for heart failure.
- Understanding the mechanisms of cardiac hypertrophy development and regression is crucial for therapeutic strategies.
- Existing models may not fully capture the dynamic changes of cardiac remodeling.
Purpose of the Study:
- To assess the utility of the cyp1a1ren-2 transgenic rat model for investigating inducible hypertension and its impact on cardiac hypertrophy.
- To evaluate the reversibility of cardiac hypertrophy in this model.
- To establish a platform for studying cardiac healing processes.
Main Methods:
- Cyp1a1ren-2 rats were administered indole-3-carbinol (I3C) to induce hypertension.
- Cardiac magnetic resonance imaging (MRI) was used to measure left ventricular mass and ejection fraction over 10 weeks.
- Telemetric recording monitored blood pressure changes during hypertension induction and regression.
Main Results:
- Induction with I3C led to a significant increase in plasma prorenin and mean blood pressure.
- Left ventricular mass increased by 39% in I3C-treated rats, with no change in ejection fraction.
- Cardiac hypertrophy regressed completely within 42 days after I3C cessation, with blood pressure returning to baseline.
Conclusions:
- The cyp1a1ren-2 transgenic rat model provides a robust system for studying inducible hypertension.
- This model facilitates the investigation of cardiac hypertrophy development and complete reversal.
- It serves as a valuable tool for exploring healing mechanisms in cardiovascular disease without surgical intervention.
