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Cardiovascular Research 1993 27(3):429-434; doi:10.1093/cvr/27.3.429
© 1993 by European Society of Cardiology
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Copyright © 1993, European Society of Cardiology

Diuretic effects on cardiac hypertrophy in the stroke prone spontaneously hypertensive rat

Francis Contard, Marina Glukhova, Françoise Marotte, Guy Narcisse, Christian Schatz, Bernard Swynghedauw, David Guez, Jane-Lyse Samuel and Lydie Rappaport

U127 INSERM, Hôpital Lariboisière, 41 bd de la Chapelle, 75010 Paris, France: F Contard, M Glukhova, F Marotte, B Swynghedauw, J-L Samuel, L Rappaport; Institut du Médicament de Tours, Saint Pierre des Corps, France: G Narcisse; Institut de Recherches Internationales Servier, Courbevoie, France: C Shatz, D Guez.

Correspondence to Dr Contard.

Objective: The aim was to compare the effects of two diuretics, indapamide and hydrochlorothiazide, on cardiac hypertrophy in stroke prone spontaneously hypertensive rats (SHR-SP). Methods: Six week old SHR-SP, on a 1% sodium chloride water intake, were treated with oral indapamide (3 mg·kg–1·d–1) or hydrochlorothiazide (20 mg·kg–1·d–l) over a 44 d period. The hypertrophic process was evaluated by classical indices and by the morphological analysis of myocyte cross sectional area, coronary artery thickness, and immunohistochemical analysis of interstitial fibrosis. Results: In the untreated SHR-SP on 1% sodium chloride, all animals developed severe hypertension and cardiac hypertrophy when compared to normotensive salt loaded WKY by 13 weeks of age. In salt loaded SHR-SP treated with indapamide or hydrochlorothiazide, systolic blood pressure was moderately decreased by the end of the treatment when compared with untreated SHR-SP, at 259(7) and 245(7) mm Hg respectively, v 300(11) mm Hg, p ≤0.05. Myocyte enlargement appears to be the main feature involved in the development of cardiac hypertrophy in the SHR-SP. By the end of treatment both indapamide and hydrochlorothiazide prevented the development of cardiac hypertrophy evaluated by heart weight to body weight ratio [4.69(0.07) and 4.61(0.08) respectively, v 5.39(0.13), p ≤ 0.001] and myocyte hypertrophy (–33% and –21% of the SHR-SP values, p ≤0.001). Myocardial interstitial fibrosis and perivascular fibrosis were practically absent in the two treated groups. Conclusions: Our results allow the characterisation of SHR-SP cardiac hypertrophy and indicate that the two types of chronic diuretic treatment prevent SHR-SP cardiac hypertrophy with a drug specific efficiency.

Cardiovascular Research 1993;27:429-434

KEYWORDS hypertension; stroke prone spontaneously hypertensive rat, diuretic, indapamide, hydrochlorothiazide, cardiovascular hypertrophy


We wish to thank Dr D Paologgi and Mrs M F Renard for hydroxyproline assay, and P Gerard and C Foulon for technical assistance, and Dr J Limas and A Barrieux for helpful discussion.


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