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 vasodilation 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.
D000818:Animals; D001160:Arterioles / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004789:Enzyme Activation; D005947:Glucose / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D010841:Pia Mater / Q000098:blood supply; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D011493:Protein Kinase C; D005947:Glucose