Diuretic effects on cardiac hypertrophy in the stroke prone spontaneously hypertensive rat.
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 x d-1) or hydrochlorothiazide (20 mg.kg-1 x d-1) 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 < or = 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 < or = 0.001] and myocyte hypertrophy (-33% and -21% of the SHR-SP values, p < or = 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.
U127 INSERM, Hôpital Lariboisière, Paris, France.
F
F
Contard
M
M
Glukhova
F
F
Marotte
G
G
Narcisse
C
C
Schatz
B
B
Swynghedauw
D
D
Guez
J L
JL
Samuel
L
L
Rappaport
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000473:pathology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000473:pathology; D004353:Drug Evaluation, Preclinical; D005355:Fibrosis; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D006973:Hypertension / Q000150:complications*; D007190:Indapamide / Q000627:therapeutic use*; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D014554:Urination / Q000187:drug effects
D006852:Hydrochlorothiazide; D007190:Indapamide