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.
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