The Effects of Antihypertensive Agents on Atherosclerosis-Related Parameters of Human Aorta Intimal Cells

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.

Amlodipine and Carvedilol Prevent Cytotoxicity in Cortical Neurons Isolated from Stroke-Prone Spontaneously Hypertensive Rats

“…Although calcium antagonists were originally developed for use in the treatment of angina pectoris, they are now used to treat other cardiovascular disorders. Amlodipine lowers intracellular cholesterol levels in smooth muscle cells of human atherosclerotic plaques and prevents cholesterol from accumulating in normal cells from patients with coronary atherosclerosis (9,26). This suggests that a reduction in the peroxidation and preservation of superoxide dismutase (SOD) may be a common mechanism behind the antiatherosclerotic effects of amlodipine (27).…”

“…Amlodipine significantly inhibited serum-induced increases in cholesterol content and cell-proliferative activity in cultured human cells (9). Another report revealed novel mechanisms in the antiproliferative effects of amlodipine in vascular smooth muscle cells (VSMC) from SHR.…”

Increased Expression and Activity of RhoA Are Associated With Increased DNA Synthesis and Reduced p27 Kip1 Expression in the Vasculature of Hypertensive Rats

“…4,5 Clinical studies indicate that traditional antihypertensive therapies are inadequate at reducing the coronary events and renal failure associated with hypertension (see review 6 ), and there is no indication that lowering blood pressure decreases atherosclerotic parameters such as smooth muscle cell proliferation. 7 Potential new targets for pharmacological regulation of vascular proliferation and migration are therefore being sought.…”

The hyperlipemic hamster ‐ a model for testing the anti‐atherogenic effect of amlodipine

“…Testing the inhibitors of CCB [24,25], inhibitors of angiotensin converting enzyme, such as captopril and fosinopril [26], and the ACAT inhibitor octimibate [27] have shown that hamster is a useful model for assessing the effects of many drugs. Studies from literature showed that amlodipine significantly lowers the intracellular cholesterol content of smooth muscle cells derived from atherosclerotic plaques [28] and restores the cholesterol enriched membrane bilayer to normal [29].…”