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Ultrasonic Assessment of Myocardial Microstructure
Published on: January 14, 2014
Myocardial changes after spironolactone in spontaneous hypertensive rats. A laser scanning confocal microscopy study
Leila Maria Meirelles Pereira1, C A Mandarim-de-Lacerda
1Laboratory of Morphometry & Cardiovascular Morphology, Biomedical Centre, Institute of Biology, State University of Rio de Janeiro, Brazil.
Insights
Spironolactone alone had limited effects on cardiac structure in hypertensive rats. Combining spironolactone with enalapril or verapamil significantly improved myocardial structure and reduced fibrosis.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Histopathology
Background:
- Spontaneously hypertensive rats (SHR) exhibit cardiac hypertrophy and fibrosis.
- Spironolactone is a mineralocorticoid receptor antagonist with potential cardioprotective effects.
- Combination therapies are often used to manage hypertension and its cardiac complications.
Purpose of the Study:
- To evaluate the effects of spironolactone monotherapy and combination therapy on cardiac structure in SHR.
- To investigate the dose-dependent effects of spironolactone on blood pressure and myocardial alterations.
- To compare the efficacy of spironolactone combined with enalapril or verapamil against monotherapy.
Main Methods:
- Laser scanning confocal microscopy was used to assess cardiac structure.
- Thirty spontaneously hypertensive rats were divided into six treatment groups over 13 weeks.
- Treatments included control, varying doses of spironolactone, spironolactone + enalapril, and spironolactone + verapamil.
Main Results:
- Spironolactone demonstrated a dose-dependent effect on blood pressure.
- High-dose spironolactone or combination therapy with enalapril partially prevented cardiac hypertrophy.
- Spironolactone monotherapy showed limited improvement, with persistent cardiac myocyte hypertrophy, fibrosis, and inflammation.
- Combination therapy with enalapril or verapamil effectively prevented myocardial structural alterations.
Conclusions:
- Spironolactone monotherapy offers limited cardioprotection against structural damage and fibrosis in SHR.
- Combining spironolactone with enalapril or verapamil enhances its efficacy in preserving myocardial structure.
- Combination therapy is a more effective strategy for mitigating cardiac remodeling in this hypertensive model.
Abstract:
The present study aims to objectivate by laser scanning confocal microscopy, the cardiac structure of the spontaneously hypertensive rats (SHR) treated with different doses of spironolactone, either alone or in combination with an angiotensin converting enzyme inhibitor or with a calcium channel blocker. Thirty SHRs were divided into six groups and treated during 13 weeks as follows: control, spironolactone (5, 10 and 30 mg/kg/day), spironolactone + enalapril and spironolactone + verapamil. Spironolactone action on the SHR blood pressure (BP) was dose-dependent. The cardiac hypertrophy was affected by the treatment with spironolactone (high dose) or a combination of spironolactone and Enalapril. The myocardial structure was less affected by the spironolactone monotherapy (at all doses) showing hypertrophied cardiac myocytes, focal areas of the reactive fibrosis, inflammatory infiltrate. The treatment with spironolactone in combination with enalapril or verapamil prevented these alterations. In conclusion, the monotherapy with spironolactone had only a limited effect in the preservation of the myocardial structure and in the attenuation of the interstitial fibrosis in SHRs, even after high dose. This action on the myocardium is more efficient when the spironolactone (even in medium dose) was associated with enalapril or verapamil.
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