Role of calcium antagonists in progression of arteriosclerosis. Evidence from animal experiments and clinical experience

Abstract

The quantitative predominance of free and total cholesterol over the amount of mural calcium is a most significant criterion of healthy human coronary arteries during the whole life span (0-90 years). However, this normal ratio increasingly changes as soon as arteriosclerotic alterations of the coronary walls set in. Accordingly, the mural calcium content steadily rises from fatty streaks over severe arteriosclerosis and, lastly, seems to reach a climax in plaques which caused lethal coronary infarction. Furthermore, the severe arteriosclerosis of human art. dorsalis pedis with gangrene (and amputation) is characterized by a tremendous calcium incorporation and absence of any mural cholesterol changes. Only in rare cases of human basilary plaques was a dangerous cholesterol incorporation in brain arterial wall found without significant elevation of serum cholesterol levels. The presented data indicate the existence of two different types of arteriosclerosis in one and the same patient and two basically different types of experimental coronary plaques according to their chemical composition, microscopic aspect and responsiveness to calcium antagonists: 1) the calcium type, developing in vitamin-D3-treated rats, and 2) the cholesterol type, represented by fatty coronary atheromata of cholesterol-fed rabbits. Coronary atheromata of cholesterol-fed New Zealand rabbits may be suitable models for coronary heart disease in rare cases of human familiar hypercholesterolemia. The formation of conventional human coronary artery plaques, however, essentially requires a progressive uptake of calcium, thereby representing a calcium dominated type of arteriosclerosis. Calcium antagonists specifically inhibit progredient mural calcium uptake in all experimental models of arteriosclerosis tested so far. However, neither in atheromatous arteries nor in afflicted organs (myocardium, liver, kidneys) of cholesterol-fed rabbits were we able to find any significant prevention of cholesterol accumulation by calcium antagonist.