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Effects of captopril on interstitial collagen in the myocardium after infarction in rats
M C Milanez1, M G Gomes, D V Vassallo
1Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Brazil.
Insights
Captopril treatment effectively reduces cardiac hypertrophy and collagen deposition following myocardial infarction. These beneficial effects on heart remodeling occur even with short-term or delayed captopril administration.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Cardiac Remodeling
Background:
- Myocardial infarction (MI) leads to heart failure via tissue loss and impaired contractility.
- Increased collagen in the extracellular matrix of surviving myocardium contributes to heart failure post-MI.
- Renin-angiotensin system activation is implicated in post-MI cardiac fibrosis.
Purpose of the Study:
- To investigate if blockade of the renin-angiotensin system with captopril can prevent post-MI myocardial hypertrophy and reactive fibrosis.
- To assess the impact of continuous, early, or late captopril therapy on cardiac remodeling after MI.
Main Methods:
- Rats underwent coronary artery ligation to induce myocardial infarction.
- Treatment groups received captopril (30 mg/kg/day) for 6 weeks, the first 3 weeks, or the last 3 weeks post-MI.
- Control groups included uninfarcted and untreated infarcted rats.
- Heart chamber hypertrophy and collagen deposition (hydroxyproline) were measured 6 weeks post-MI.
Main Results:
- Untreated MI rats showed significant increases in right and left ventricular hydroxyproline content and myocardial weight.
- Captopril treatment for 6 weeks significantly reduced ventricular hydroxyproline and myocardial weight compared to untreated MI rats.
- Protein concentration decreased in infarcted ventricles, an effect enhanced by captopril.
- Both early and late short-term captopril therapies showed lesser, but still observable, effects on hypertrophy and collagen content.
Conclusions:
- Captopril effectively reduces post-MI hypertrophy and collagen deposition in surviving myocardium.
- Therapeutic benefits of captopril are observed even with short-term administration, either immediately after MI or later in the remodeling process.
Background:
Myocardial infarction is an important cause of heart failure because it cause tissue loss and contractility disturbances. In chronically infarcted hearts the increase in the collagen content in the extracellular matrix of the surviving viable myocardium has been considered a major factor contributing to development of heart failure. Postinfarction neuroendocrine activation involving the renin-angiotensin system has been implicated in this cardiac fibrosis.
Methods And Results:
As collagen synthesis and degradation are dynamic processes and postinfarction remodeling is a time-dependent phenomenon, rats submitted to coronary artery ligation to produce myocardial infarction were treated with captopril after infarction (30 mg/kg, intraperitoneally, daily) to investigate whether blockade of the renin-angiotensin system can prevent postinfarction myocardial hypertrophy and reactive fibrosis. Groups of rats with myocardial infarction were treated with captopril throughout the protocol period (6 weeks), or during the first 3 weeks after infarction (early therapy), or only during the last 3 weeks of the protocol (late therapy). Untreated groups of rats with or without myocardial infarction were used as control subjects. All animals were killed 6 weeks after surgery to evaluate hypertrophy of heart chambers and collagen deposition in the right ventricle wall and in surviving left ventricular muscle. Protein and hydroxyproline concentrations were assayed biochemically in these tissue homogenates. Only rats with an infarct covering 20 to 40% of the left ventricular surface were included in the study. In the control uninfarcted group (n = 12), hydroxyproline content was 152 +/- 12 micrograms in the right ventricle and 370 +/- 30 micrograms in the left ventricle. These values increased (P < .05) to 232 +/- 13 and 630 +/- 46 micrograms, respectively, in the group with myocardial infarction (n = 8) without treatment. These values were significantly reduced (P < .05) to 160 +/- 9 micrograms in the right ventricle and 520 +/- 40 micrograms in the left ventricle in the group with myocardial infarction treated with captopril for 6 weeks. The percentage decreases in collagen content and myocardial weight produced by captopril were similar. Thus, hydroxyproline concentration (mg hydroxyproline muscle), which increases significantly in both ventricles after myocardial infarction, was not modified by captopril therapy. Protein concentration in the right and left ventricular muscles decreased after myocardial infarction. This decrease was enhanced in the infarcted groups submitted to captopril treatment, mainly in the group treated for 6 weeks. Lesser effects on hypertrophy and hydroxyproline content were observed in the groups of rats treated with captopril in only the earlier or later phase of infarction.
Conclusions:
It is concluded that captopril reduces similarly postinfarction hypertrophy and collagen deposition in surviving myocardium. These effects, although less intense, also occur when the drug is used for a short period immediately after myocardial infarction or when used later, when ventricular remodeling is almost fully developed.