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Effects of enalapril and hydrochlorothiazide on the salt-induced cardiac and renal hypertrophy in normotensive rats

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Abstract

Recent studies have shown that, not only in hypertensive animals but even in normotensive rats, dietary salt (sodium chloride) produces a dose-related increase in the left ventricular and renal mass. In the present study the effects of the angiotensin converting enzyme inhibitor (ACEI) enalapril and the thiazide-type diuretic, hydrochlorothiazide, on the development of the salt-induced left ventricular and kidney hypertrophy were examined in normotensive Wistar-Kyoto and Wistar rats. A high intake of sodium chloride (6% of the dry weight of the chow to mimic the level found in many human food items) during eight weeks produced a marked increase in the mass of the left ventricle and the kidneys in both rat strains with little or no effect on blood pressure. The cardiac hypertrophy correlated strongly with the renal hypertrophy. These salt-induced changes in the heart and in the kidneys were completely blocked by hydrochlorothiazide, while enalapril was devoid of any significant effects during the high-salt diet. However, during a low-salt diet enalapril, but not hydrochlorothiazide, effectively lowered the blood pressure and decreased the left ventricular mass of the normotensive rats. There was a 3- to 4-fold increase in the urinary excretion of calcium during the high intake of sodium chloride. Hydrochlorothiazide decreased the urinary excretion of calcium even during the low salt diet, and it completely blocked the salt-induced hypercalciuria. Enalapril had no significant effect on the urinary calcium excretion. During the low-salt diet hydrochlorothiazide increased the calcium and decreased the potassium concentration in the heart while enalapril increased the phosphorus concentration.

In conclusion, a high intake of sodium chloride produced hypertrophy both in the heart and in the kidneys, even in the absence of a rise in blood pressure. Salt also remarkably increased the urinary calcium excretion. These harmful effects of salt were blocked by the thiazide diuretic hydrochlorothiazide but not by the ACEI enalapril. However, this study does not allow to make any direct comparison between the effects of enalapril and hydrochlorothiazide.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, University of Helsinki, P.O. box 8 (Siltavuorenpenger 10), SF-00014, University of Helsinki, Finland

    Eero M. A. Mervaala, Heikki Vapaatalo & Heikki Karppanen

  2. Mila Ltd., Sirrikuja 413, SF-00940, Helsinki, Finland

    Juha Laakso

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  1. Eero M. A. Mervaala
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  3. Heikki Vapaatalo
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Correspondence to: E. Mervaala at the above address

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Mervaala, E.M.A., Laakso, J., Vapaatalo, H. et al. Effects of enalapril and hydrochlorothiazide on the salt-induced cardiac and renal hypertrophy in normotensive rats. Naunyn-Schmiedeberg's Arch Pharmacol 350, 416–425 (1994). https://doi.org/10.1007/BF00178961

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