© 1993 by European Society of Cardiology
Copyright © 1993, European Society of Cardiology
Diuretic effects on cardiac hypertrophy in the stroke prone spontaneously hypertensive rat
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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