Protective effects of various calcium antagonists against experimental arteriosclerosis

Arterial walls altered by sclerotic processes accumulate lipids (particularly cholesterol) and calcium. Whereas the accumulation of lipids has long been incriminated as the major pathogenic factor involved in arteriosclerosis, concomitant arterial calcium overload has been considered of secondary importance. Using various animal models and specific calcium antagonists as experimental tools, we have shown the crucial role of excessive calcium uptake into arterial walls in the pathogenesis of arteriosclerotic lesions. Anticalcinotic vasoprotection with calcium antagonists has been demonstrated using light and electron microscopy, radiocalcium uptake experiments and calcium analyses with atomic absorption spectroscopy. The new 1,4-dihydropyridine calcium antagonist amlodipine has been shown to inhibit calcium accumulation in the internal elastic membrane of abdominal arteries of NaCl-loaded salt-sensitive Dahl-S rats, and consequently also exerts protective effects against arteriosclerotic lesions, shown particularly in the distal mesenteric artery branches. Formation of human coronary plaques is marked by a substantial local uptake of calcium, whereas there is a large overlap in the mural cholesterol content of healthy coronary arteries and plaques. Experimental findings in animals and with human tissue indicate that calcium antagonists such as amlodipine may provide a new approach to the prophylaxis of coronary artery lesions.