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 endothelium-dependent reactivity of rat cerebral arterioles. Our second goal was to investigate a possible mechanism for impaired reactivity during acute hyperglycemia. Diameter of pial arterioles was measured during suffusion with ADP, acetylcholine, histamine, N-methyl-D-aspartate (NMDA), and nitroglycerin before and during application of a suffusate containing D-glucose (5, 10, 20, and 25 mM). ADP, acetylcholine, histamine, NMDA, and nitroglycerin produced dose-related vasodilatation before application of D-glucose. Vasodilatation in response to the agonists was not altered by 5 and 10 mM D-glucose. In contrast, vasodilatation in response to ADP, acetylcholine, histamine, and NMDA was impaired during application of 20 and 25 mM D-glucose. Dilatation in response to nitroglycerin was not altered. Application of the protein kinase C inhibitor calphostin C (1.0 nM) or chelerythrine (10 nM) restored endothelium-dependent vasodilatation during application of 25 mM D-glucose. Thus acute hyperglycemia impairs endothelium-dependent responses of cerebral arterioles via the activation of protein kinase C.