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

• Published in: Cardiovascular research 1993-03, Vol.27 (3), p.429-434
• Main Authors: Contard, Francis, Glukhova, Marina, Marotte, Françoise, Narcisse, Guy, Schatz, Christian, Swynghedauw, Bernard, Guez, David, Samuel, Jane-Lyse, Rappaport, Lydie
• Format: Article
• Language: English
• Subjects: Animals; Antihypertensive agents; Biological and medical sciences; Blood Pressure - drug effects; Cardiomegaly - pathology; Cardiomegaly - prevention & control; cardiovascular hypertrophy; Cardiovascular system; Coronary Vessels - pathology; diuretic; Drug Evaluation, Preclinical; Fibrosis; hydrochlorothiazide; Hydrochlorothiazide - therapeutic use; hypertension; Hypertension - complications; indapamide; Indapamide - therapeutic use; Medical sciences; Myocardium - pathology; Organ Size; Pharmacology. Drug treatments; Random Allocation; Rats; Rats, Inbred SHR; Rats, Inbred Strains; stroke prone spontaneously hypertensive rat; Urination - drug effects
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1093/cvr/27.3.429

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