Comparative effects of indapamide and hydrochlorothiazide on cardiac hypertrophy and vascular smooth-muscle phenotype in the stroke-prone, spontaneously hypertensive rat.
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.
Contard
F
F
Unité 127 INSERM, Hôpital Lariboisière, Paris, France.
Glukhova
M
M
Sabri
A
A
Marotte
F
F
Sartore
S
S
Narcisse
G
G
Schatz
C
C
Guez
D
D
Rappaport
L
L
Samuel
J L
JL
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000209:etiology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology; D006852:Hydrochlorothiazide / Q000494:pharmacology / Q000627:therapeutic use*; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D007190:Indapamide / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D010641:Phenotype; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D006852:Hydrochlorothiazide; D007190:Indapamide