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Study of antiatherogenic properties of indapamide in a pharmacologic model
E Lebrillant1, M J Roulet, R Robert
1Cerep, Celle L'Evescault, France.
Abstract:
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.
Insights
Indapamide demonstrated antiatherogenic effects in a rabbit model, reducing plaque formation at a low dose. Higher indapamide doses and hydrochlorothiazide did not show similar benefits.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Atherosclerosis Research
Background:
- Atherosclerosis is a major cause of cardiovascular disease.
- Developing effective antiatherogenic therapies is crucial.
- Rabbit models provide a platform for studying atherosclerosis development and treatment.
Purpose of the Study:
- To investigate the antiatherogenic potential of indapamide.
- To compare indapamide's efficacy against flunarizine and hydrochlorothiazide.
- To determine the dose-dependent effects of indapamide on atheromatous plaque formation.
Main Methods:
- A rabbit model of atherosclerosis was induced using carotid electrical stimulation and a cholesterol-rich diet.
- Animals were treated with indapamide (0.3, 1, 3 mg/kg/day), hydrochlorothiazide (20 mg/kg/day), or flunarizine (25 mg/kg/day).
- Image analysis quantified the number of cell layers (NCL) and intima/media area ratio (I/M) to assess plaque development.
Main Results:
- Indapamide at 0.3 mg/kg/day significantly reduced NCL and I/M, indicating an antiatherogenic effect.
- Indapamide showed greater efficacy than flunarizine in reducing plaque markers.
- Hydrochlorothiazide did not exhibit any antiatherogenic activity; higher indapamide doses showed reduced efficacy.
Conclusions:
- Indapamide exhibits significant antiatherogenic properties in a rabbit model, particularly at lower doses.
- The study highlights indapamide's potential as a therapeutic agent for atherosclerosis.
- Further research is warranted to elucidate the mechanisms behind indapamide's dose-dependent effects and potential therapeutic applications.