Cardiovascular drugs and atherosclerosis: effects of calcium antagonists, beta-blockers, and nitrates on atherosclerotic characteristics of human aortic cells.

Primary cell culture derived from atherosclerotic plaque of human aorta was used to assess direct effects of calcium antagonists, beta-blockers, and nitrates on vessel wall cells. Within 24 h, calcium antagonists (verapamil, nifedipine, darodipine, isradipine, diltiazem, etc.) reduced the cholesterol level in cultured cells. Furthermore, these agents decreased the incorporation of [3H]thymidine. Thus, the calcium antagonists manifested direct antiatherosclerotic action in culture by normalizing major manifestations of atherosclerosis at the cellular level. On the other hand, beta-blockers (propranolol, alprenolol, metoprolol, atenolol, pindolol, and timolol) caused a 1.5- to twofold rise in cholesterol level of cultured cells and stimulated their proliferation. Nitrates (nitroglycerin, isosorbide dinitrate, and nitroprusside) had no effect on atherosclerotic characteristics. Within 2-4 h after a single dose of oral administration of beta-blocker (propranolol), patients' blood plasma turned atherogenic, i.e., its addition to culture-induced cholesterol accumulation and stimulated proliferation. At the same time, blood plasma of patients who received calcium antagonists (verapamil and nifedipine) acquired antiatherosclerotic properties manifested in its ability to lower the intracellular cholesterol level and inhibit proliferative activity of cultured cells. These findings allow the assumption that not only in vitro, but in vivo as well, calcium antagonists and beta-blockers are antiatherosclerotic and atherogenic drugs, respectively.