Study of antiatherogenic properties of indapamide in a pharmacologic model.
A localized atheromatous plaque was induced in rabbits after transmural electrical stimulation of the carotid and a cholesterol-rich diet (1.33% cholesterol) for 4 weeks. This model was used to investigate the antiatherogenicity of indapamide. The treatment given per os started 14 days before the stimulation period. Animals were divided into six groups: group 1 (control) received gelatin 2%, group 2 received hydrochlorothiazide at 20 mg/kg/day, group 3 was treated with flunarizine at 25 mg/kg/day, and groups 4, 5, and 6 received indapamide at 0.3, 1, and 3 mg/kg/day, respectively. During the experimental period, all rabbits showed similar weight gain, regardless of the treatment. Image analysis showed an antiatherogenic effect for indapamide (0.3 mg/kg/day) characterized by a reduction in the number of cell layers (NCL; 10.5 +/- 1.8 vs. 18.0 +/- 2.9; p < 0.05) and in the intima/media area ratio (I/M; 17.5 +/- 4.5 vs. 42.7 +/- 7.0%; p < 0.01). Indapamide appeared to be more active than the reference drug flunarizine (NCL = 14.2 +/- 2.5, N.S.; I/M = 24.5 +/- 4.3, p < 0.05). The maximum effect occurred at the lowest dose tested (0.3 mg/kg/day). The reason for the loss of antiatherogenic activity of indapamide at higher doses is discussed. Hydrochlorothiazide did not show any effect on the formation of the atheromatous plaque.
Lebrillant
E
E
Cerep, Celle L'Evescault, France.
Roulet
M J
MJ
Robert
R
R
Schiavi
P
P
Guez
D
D
Jean
T
T
D000818:Animals; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000473:pathology; D001485:Basement Membrane / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002791:Cholesterol, Dietary; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005444:Flunarizine / Q000494:pharmacology; D006852:Hydrochlorothiazide / Q000494:pharmacology; D007091:Image Processing, Computer-Assisted; D007190:Indapamide / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D011817:Rabbits; D017539:Tunica Intima / Q000187:drug effects
D002791:Cholesterol, Dietary; D006852:Hydrochlorothiazide; D007190:Indapamide; D005444:Flunarizine