Calcium antagonists and cellular mechanisms of glomerulosclerosis and atherosclerosis

Glomerulosclerosis is the final common glomerular lesions in many renal diseases. The histological features of focal glomerulosclerosis resemble the lesion of atherosclerosis and may indicate a parallel pathogenesis. Central to the pathogenesis of atherosclerosis is the interaction of blood cells and endothelial cells with subsequent proliferation of smooth muscle cells and enhanced production of collagen. The mechanisms that appear to be responsible for this increased proliferative response are growth factors, cytokines, and local alterations in the extracellular matrix. The corresponding counterparts in glomerulosclerosis include mesangial expansion with mesangial cell proliferation, mesangial foam cell accumulation, tissue necrosis, and eventual sclerosis. Substances that interfere with the interaction between the different cell types, such as endothelial cells, macrophages, and platelets, and with the proliferative responses of both vascular and mesangial cells may be of therapeutic value in both diseases. Calcium antagonists interfere with the cellular activation induced by growth factors and vasoactive hormones and, in platelets, they decrease aggregation and the secretion of thromboxane from these cells. In addition to their relaxant effect, calcium antagonists diminish the proliferative response of vascular smooth muscle and mesangial cells to growth factors while, in macrophages, production of superoxides is decreased after incubation with calcium antagonists. In mesangial cells it has been demonstrated that calcium antagonists decrease the expression and secretion of matrix proteins. That these cellular mechanisms result in an anti-atherosclerotic effect in vivo has been shown by various animal studies, and a beneficial effect of calcium antagonists on the progression of glomerulosclerosis has also been observed.(ABSTRACT TRUNCATED AT 250 WORDS)