Acute effects of glucose on reactivity of the cerebral
microcirculation: role of activation of protein kinase c.
Mayhan, William G., and Kaushik P. Patel.
Department of Physiology and Biophysics, University of Nebraska
Medical Center, Omaha, Nebraska 68198-4575
APStracts 2:0172H, 1995.
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 5'-adenosine diphosphate (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.
Received 5 December 1994; accepted in final form 17 April 1995.
APS Manuscript Number H1066-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 2 May 1995.