Ca2+ mobilization in the aortic endothelium in streptozotocin-induced diabetic and cholesterol-fed mice

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Abstract
Experiments were performed to compare Ca2+ mobilization in the aortic endothelium in streptozotocin (STZ)‐induced diabetic and cholesterol‐fed mice with that in age‐matched controls. The intracellular free Ca2+ ([Ca2+]i) in the fura PE‐3 loaded endothelium of aortic rings was dose‐dependently increased by cumulative administration of acetylcholine (ACh). ACh caused a transient rise in [Ca2+]i in Ca2+‐free medium. The ACh‐induced increase in [Ca2+]i in normal or Ca2+‐free medium was significantly weaker in both STZ‐induced diabetic and cholesterol‐fed mice. The weaker [Ca2+]i response in Ca2+‐containing medium in STZ‐induced diabetic and cholesterol‐fed mice was normalized by chronic administration of cholestyramine. The increased low density lipoprotein (LDL) levels seen in both STZ‐induced diabetic and cholesterol‐fed mice were normalized by the same chronic administration of cholestyramine (300 mg kg−1, p.o. daily for 10 weeks). Chronic administration of cholestyramine had no effect on the plasma glucose level. Lysophosphatidylcholine (LPC) decreased the [Ca2+]i responses to ACh in the aortic endothelium from normal mice. These results suggest that ACh increases both Ca2+ influx and Ca2+ release from storage in the aortic endothelium. The weaker [Ca2+]i influx seen in the endothelium of aortae from both STZ‐induced diabetic and cholesterol‐fed mice was improved by the chronic administration of cholestyramine, and we suggest that this improvement is due, at least in part, to a lowering of the plasma LDL level. It is further suggested that LPC may have an important influence over Ca2+ mobilization in the endothelium. British Journal of Pharmacology (1998) 123, 1509–1516; doi:10.1038/sj.bjp.0701754

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