Role of calcium in arteriosclerosis--experimental evaluation of antiarteriosclerotic potencies of Ca antagonists. Study Group for Calcium Antagonism.
Chemical microanalyses of conventional human coronary artery plaques (stages I-III [WHO]) revealed the correlation between progressive mural Ca overload up to excessive degrees, and the severity of plaque formation, whereas only small amounts of cholesterol were found, even in complicated lesions. The pathogenetic role of Ca was tested in three types of experimental arteriosclerosis and atheromatosis, using Ca antagonists (verapamil, nitrendipine, diltiazem) as research tools: 1) The Ca type, in vitamin D3 plus nicotine-treated rats; 2) the cholesterol type, in cholesterol-fed New Zealand rabbits; 3) mixed types, in SHRs and NaCl-fed Dahl-S rats. Types (1) and (3) were demonstrated to be governed by a progressive arterial Ca uptake that could be established already in early lesions. The increased mural Ca supply promoted cellular necroses, migration, and proliferation, as well as calcification and degradation of elastic fibers. Ca antagonists prevented the increased Ca incorporation into arterial walls and inhibited the development of experimental arterioscleroses of types (1) and (3). Ca antagonists did not protect coronary arteries of cholesterol-fed rabbits (type [2]) from occlusive cholesterol accumulation. The data suggest an important pathogenetic role of Ca and pronounced antiarteriosclerotic potencies of Ca antagonists in Ca-dominated types of experimental arteriosclerosis. The significance of the present results for pathophysiology and therapy of conventional human arteriosclerosis remains to be clarified.
Fleckenstein-Grün
G
G
Physiology Institute, University of Freiburg, FRG.
Thimm
F
F
Frey
M
M
Czirfusz
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D002136:Calcium, Dietary / Q000008:administration & dosage; D002784:Cholesterol / Q000378:metabolism; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D011817:Rabbits; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley
D002121:Calcium Channel Blockers; D002136:Calcium, Dietary; D002784:Cholesterol; D002118:Calcium