EFFECT OF CALCIUM-CHANNEL BLOCKERS ON INTRACELLULAR CALCIUM ACCUMULATION

Protection against acute renal failure by calcium channel blockers inc lude radiocontrast agent, cyclosporin, aminoglycosides, amphotericin B , cisplatin nephrotoxicity, and ischaemia-induced toxicity. Calcium ov erload occurs in ischaemic cells. The type of calcium channel blocker influences the potential effect on protection against nephrotoxicity. A number of growth factors and hormones induce cellular activation by increasing calcium concentrations. Calcium channel blockers interfere with activation of different cell types, e.g. decrease platelet aggreg ation, macrophage activation, platelet-activating factor release and a lso proliferative response of vascular smooth muscle and mesangial cel ls. Uraemia is also a state of calcium accumulation. Increase of intra cellular calcium [Ca2+]i in PMNLs is associated with deactivation. Tre atment with calcium channel blockers normalizes elevated PMNL [Ca2+]i and improves functional parameters of PMNLs. Normalization of enhanced [Ca2+]i of PMNLs can also be achieved with effective 1,25(OH)2 vitami n D3 therapy by lowering PTH. Uraemia is also a state of insulin resis tance. Elevated levels of [Ca2+]i in insulin target cells diminish sen sitivity to insulin at the postbinding site. Therapeutic manoeuvres pr eventing the increase of cytosolic calcium may improve insulin resista nce.