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Effects of chlorthalidone on ventricular hypertrophy in deoxycorticosterone acetate-salt hypertensive rats
A M Cabral1, F B Carvalhinho, E C Vasquez
1Department of Physiological Sciences, Biomedical Center, UFES, Vitoria, Brazil.
Insights
Long-term chlorthalidone treatment effectively prevents or reduces cardiac hypertrophy and arterial hypertension in rats. This diuretic
Area of Science:
- Cardiovascular Pharmacology
- Renal Physiology
Background:
- Diuretics are standard for hypertension but their efficacy against hypertensive cardiac hypertrophy is unproven.
- Cardiac hypertrophy is a significant complication of uncontrolled hypertension.
Purpose of the Study:
- To investigate the effects of long-term chlorthalidone administration on the development and reversal of cardiac hypertrophy in a rat model of deoxycorticosterone acetate (DOCA)-salt-induced hypertension.
Main Methods:
- Rats received DOCA and salt to induce hypertension and cardiac hypertrophy.
- Chlorthalidone was administered either preventively (during DOCA treatment) or therapeutically (after DOCA initiation).
- Cardiac mass, protein content, arterial pressure, plasma sodium, and cardiac sympathetic tone were assessed.
Main Results:
- Chlorthalidone significantly reduced or prevented ventricular hypertrophy, evidenced by decreased ventricular mass and cardiac protein.
- Both preventive and therapeutic chlorthalidone regimens attenuated arterial hypertension.
- Chlorthalidone normalized or decreased elevated plasma sodium and cardiac sympathetic tone observed in DOCA-salt rats.
Conclusions:
- Long-term chlorthalidone treatment is effective in preventing and reducing cardiac hypertrophy associated with arterial hypertension in rats.
- The mechanisms may involve reduced plasma sodium and/or decreased cardiac sympathetic tone, warranting further investigation.
Abstract:
Diuretics have been the mainstay of long-term treatment of hypertension, but there is no evidence suggesting that diuretics may be effective in reducing cardiac hypertrophy associated with hypertension. Thus, the present study was carried out to elucidate if long-term treatment with chlorthalidone (8 mg per animal per day added to food) affects the development of and reverses the ventricular hypertrophy in deoxycorticosterone acetate (DOCA) (8 mg/kg SC twice a week)-salt hypertensive rats. Chlorthalidone was given to one group during all 20 days of DOCA administration (preventive regimen) and to another group 20 days after DOCA treatment was initiated until the 40th day (therapeutic regimen). Chlorthalidone was found to reduce or prevent the development of ventricular hypertrophy, as assessed by a reduction in ventricular mass and cardiac protein as well as arterial hypertension. Both chlorthalidone regimens prevented the increase or induced a significant decrease in the plasma concentration of sodium and in cardiac sympathetic tone, which were both increased in DOCA-salt-treated rats. These data provide evidence that long-term chlorthalidone treatment is effective in preventing or reducing ventricular hypertrophy along with arterial hypertension. However, whether this is due to a reduction in plasma sodium or other additional mechanisms, such as a reduction in cardiac sympathetic tone, remains to be determined.