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Comparative effects of indapamide and hydrochlorothiazide on cardiac hypertrophy and vascular smooth-muscle phenotype in the stroke-prone, spontaneously hypertensive rat.

Abstract
The effects of two diuretics, indapamide (3 mg/kg/day) and hydrochlorothiazide (20 mg/kg/day), were analyzed over a 44-day period on the cardiovascular hypertrophy of stroke-prone spontaneously hypertensive rats (SHR-SP). Untreated SHR-SP developed severe hypertension and cardiac hypertrophy when compared to normotensive Wistar-Kyoto (WKY) rats after 8 weeks on 1% sodium chloride. In diuretic-treated animals, systolic blood pressure was moderately decreased by the end of the treatment when compared with untreated SHR-SP (-13 and -18%, respectively, p < or = 0.05). Morphometric analysis of myocyte cross-sectional areas evidenced that indapamide was the most effective in preventing myocyte hypertrophy (-33%, p < or = 0.0001). Small coronary artery wall thickness was efficiently prevented in the two treated groups, but medial hypertrophy was prevented by hydrochlorothiazide only. Among markers of smooth-muscle cell phenotype (contractile or extracellular matrix proteins) EIIIA-fibronectin (FN), one FN cellular isoform, was shown to be the most sensitive marker by an immunohistochemical technic. Medial expression of EIIIA-FN, which was characteristic of SHR-SP coronary arteries, was prevented by the two treatments. The two diuretic treatments, despite similar effects on blood pressure and smooth-muscle phenotype, prevent SHR-SP cardiovascular hypertrophy with a drug-specific efficiency.
AuthorsF Contard, M Glukhova, A Sabri, F Marotte, S Sartore, G Narcisse, C Schatz, D Guez, L Rappaport, J L Samuel
JournalJournal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 22 Suppl 6 Pg. S29-34 ( 1993) ISSN: 0160-2446 [Print] United States
PMID7508058 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Hydrochlorothiazide
  • Indapamide
Topics
  • Animals
  • Blood Pressure (drug effects)
  • Cardiomegaly (etiology, prevention & control)
  • Coronary Vessels (drug effects, pathology)
  • Hydrochlorothiazide (pharmacology, therapeutic use)
  • Hypertension (complications, drug therapy)
  • Indapamide (pharmacology, therapeutic use)
  • Male
  • Muscle Contraction (drug effects)
  • Muscle, Smooth, Vascular (drug effects, pathology, physiopathology)
  • Myocardium (pathology)
  • Phenotype
  • Random Allocation
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY

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