SUMMARY AND PERSPECTIVE We demonstrated two kinds of impairing effect of glucose overload on endothelial Ca2+ mobilization; i.e., 02- mediated and protein kinase C-mediated ones. As already mentioned in the previous sections, endothelium-dependent vasodilation was impaired in aorta by the hyperglycemia-induced production of 02- (Tesfamariam & Cohen, 1992). In contrast, vasodilation in response to agonists such as acetylcholine and histamine was impaired by hyperglycemic condition in cerebral microvessels by the production of protein kinase C (Mayhan & Patel, 1995). Our observations happened to support these reports; i.e.,02-was responsible for glucose overload-induced impairment of Ca2+ mobilization in aortic endothelium and protein kinase C in brain microvascular endotheluim. However, because each mechanism affects Ca2+ mobilization in a quite different mauler, we suppose that this does not simply imply the site-specificity of the impairing action of glycose overload, but is due to the difference of Ca2+ mobilization mechanism. In other words,02- mainly affects Ca2+ pathways such as channels and pumps, and protein kinase C affects the signaling cascade which is related to Ca2+ mobilization. As summarized above, many Ca2+ mobilizing pathways, which are regulated by various biochemical and biomechanical stimulation, are involved in the regulation of endothelial [Ca2+]i. However, the details of such Ca2+mobilizing mechanism are not fully clarified. For instance, it is not known whether the cyclic AMP-mediated Ca2+ release observed in brain microvascular endothelium plays a significant role also in other vessels such as aortic endothelium. Therefore, the detailed clarification of the mechanisms of Ca2+ mobilization in vascular endothelium has an essential importance in vascular biology not only for physiological reason but also for pathophysiological reason.
Acetylcholine ; Aorta ; Biology ; Brain ; Calcium* ; Endothelial Cells* ; Endothelium ; Endothelium, Vascular ; Glucose* ; Histamine ; Homeostasis* ; Microvessels ; Protein Kinase C ; Protein Kinases ; Vasodilation