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The effects of antihypertensive agents on atherosclerosis-related parameters of human aorta intimal cells
A N Orekhov1, V V Tertov, E M Pivovarova
1Institute of Experimental Cardiology, Cardiology Research Center, Moscow, Russia.
Abstract:
Four antihypertensive agents - amlodipine, verapamil, propranolol and perindoprilat - were studied in human cell cultures. Antiatherogenic activity was investigated using uninvolved human aortic smooth muscle intima cells and atherogenic serum obtained from patients with coronary atherosclerosis. Amlodipine and verapamil significantly inhibited serum-induced increases in cholesterol content, cell-proliferative activity and protein synthesis in the cultured cells. Propranolol increased all three parameters, while perindoprilat had no effects. In addition, amlodipine and verapamil significantly lowered the intracellular cholesterol content of smooth muscle cells derived from atherosclerotic plaque and inhibited cell proliferation and protein synthesis. Propranolol increased all of these parameters, while perindoprilat produced no effects. The antiatherogenic and antiatherosclerotic actions of verapamil and amlodipine were confirmed in an ex vivo model. These studies demonstrated a beneficial antiatherosclerotic effect of amlodipine that was greater than that of verapamil. Perindoprilat had a neutral effect on atherosclerotic parameters, while the action of propranolol appeared to be potentially detrimental.
Insights
Amlodipine and verapamil show antiatherogenic effects by reducing cholesterol and protein synthesis in cells. Propranolol worsened these parameters, while perindoprilat had no effect.
Area of Science:
- Cardiovascular Pharmacology
- Atherosclerosis Research
Background:
- Atherosclerosis is a complex disease involving lipid accumulation and smooth muscle cell proliferation.
- Antihypertensive agents are widely used, but their direct effects on atherosclerotic processes require further investigation.
Purpose of the Study:
- To evaluate the antiatherogenic and antiatherosclerotic potential of four antihypertensive drugs: amlodipine, verapamil, propranolol, and perindoprilat.
- To compare the effects of these agents on human aortic smooth muscle cells and in an ex vivo model.
Main Methods:
- Human aortic smooth muscle cells and serum from patients with coronary atherosclerosis were used in cell culture experiments.
- Intracellular cholesterol content, cell proliferation, and protein synthesis were measured.
- An ex vivo model was employed to confirm antiatherosclerotic actions.
Main Results:
- Amlodipine and verapamil significantly inhibited serum-induced increases in cholesterol, proliferation, and protein synthesis.
- Propranolol increased these parameters, indicating a potentially detrimental effect.
- Perindoprilat demonstrated a neutral effect on all measured atherosclerotic parameters.
- Amlodipine exhibited a greater antiatherosclerotic effect than verapamil in ex vivo studies.
Conclusions:
- Amlodipine and verapamil possess significant antiatherogenic and antiatherosclerotic properties.
- The antiatherosclerotic effect of amlodipine is more pronounced than that of verapamil.
- Propranolol may have detrimental effects on atherosclerotic processes, while perindoprilat appears neutral.