ACUTE EFFECTS OF GLUCOSE ON REACTIVITY OF CEREBRAL MICROCIRCULATION -ROLE OF ACTIVATION OF PROTEIN-KINASE-C

Our first goal was to determine whether acute hyperglycemia alters end othelium-dependent reactivity of rat cerebral arterioles. Our second g oal was to investigate a possible mechanism for impaired reactivity du ring acute hyperglycemia. Diameter of pial arterioles was measured dur ing suffusion with ADP, acetylcholine, histamine, N-methyl-D-aspartate (NMDA), and nitroglycerin before and during application of a suffusat e containing D-glucose (5, 10, 20, and 25 mM). ADP, acetylcholine, his tamine, NMDA, and nitroglycerin produced dose-related vasodilatation b efore application of D-glucose. Vasodilatation in response to the agon ists was not altered by 5 and 10 mM D-glucose. In contrast, vasodilata tion in response to ADP, acetylcholine, histamine, and NMDA was impair ed during application of 20 and 25 mM D-glucose. Dilatation in respons e to nitroglycerin was not altered. Application of the protein kinase C inhibitor calphostin C (1.0 nM) or chelerythrine (10 nM) restored en dothelium-dependent vasodilatation during application of 25 mM D-gluco se. Thus acute hyperglycemia impairs endothelium-dependent responses o f cerebral arterioles via the activation of protein kinase C.