The possible role of endothelial dysfunction in early stages of uncomplicated diabetes mellitus was investigated in porcine aortic endothelial cells. Prolonged exposure to various D-glucose concentrations resulted in concentration-dependent amplification of agonist-induced Ca2+ mobilization, whereas L-glucose and D-mannitol failed to mimic the effect of D-glucose. This stimulatory effect of high D-glucose on endothelial Ca2+ mobilization could be antagonized by coincubation with cytochalasin B, which prevented D-glucose uptake into the cells. In agreement with its effect on agonist-induced Ca2+ response, prolonged preincubation with pathological D-glucose concentrations amplified formation of endothelium-derived relaxing factor, which is well established to be strictly attributable to increases in endothelial free Ca2+. In contrast to endothelium-derived relaxing factor formation stimulated by receptor-interacting autacoids, preincubation with high D-glucose failed to modulate A 23,187-induced endothelium-derived relaxing factor formation, which is attributable to unphysiological increases in endothelial free Ca2+ by this ionophore. Similar to its effect on D-glucose-mediated amplification of agonist-stimulated Ca2+ mobilization, cytochalasin B abolished the stimulatory effect of high D-glucose on endothelium-derived relaxing factor formation. We therefore suggest that prolonged exposure to pathological high D-glucose concentrations results in an enhanced endothelium-derived relaxing factor formation caused by amplification of agonist-stimulated Ca2+ mobilization in endothelial cells. This mechanism may be of particular importance representing a possible basis of pathological vasodilation and reduced peripheral resistance in early stages of diabetes mellitus.
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Original Articles|
October 01 1993
Exposure To Elevated D-Glucose Concentrations Modulates Vascular Endothelial Cell Vasodilatory Response
Wolfgang F Graier;
Wolfgang F Graier
Institute of Pharmacology and Toxicology and the Department of Internal Medicine, University Graz
Graz, Austria
Dalton Cardiovascular Research Center, University of Missouri
Columbia, Missouri
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Thomas C Wascher;
Thomas C Wascher
Institute of Pharmacology and Toxicology and the Department of Internal Medicine, University Graz
Graz, Austria
Dalton Cardiovascular Research Center, University of Missouri
Columbia, Missouri
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Lydia Lackner;
Lydia Lackner
Institute of Pharmacology and Toxicology and the Department of Internal Medicine, University Graz
Graz, Austria
Dalton Cardiovascular Research Center, University of Missouri
Columbia, Missouri
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Hermann Toplak;
Hermann Toplak
Institute of Pharmacology and Toxicology and the Department of Internal Medicine, University Graz
Graz, Austria
Dalton Cardiovascular Research Center, University of Missouri
Columbia, Missouri
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Günter J Krejs;
Günter J Krejs
Institute of Pharmacology and Toxicology and the Department of Internal Medicine, University Graz
Graz, Austria
Dalton Cardiovascular Research Center, University of Missouri
Columbia, Missouri
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Walter R Kukovetz
Walter R Kukovetz
Institute of Pharmacology and Toxicology and the Department of Internal Medicine, University Graz
Graz, Austria
Dalton Cardiovascular Research Center, University of Missouri
Columbia, Missouri
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Address reprint requests to Dr. Wolfgang F. Graier, Institute of Pharmacology and Toxicology, University Graz, Universitatsplatz 2, A-8010 Graz, Austria. Address correspondence to Dr. Wolfgang F. Graier, Dalton Cardiovascular Research Center, Department of Physiology, University of Missouri, Columbia, MO, 65211.
Diabetes 1993;42(10):1497–1505
Article history
Received:
November 10 1992
Revision Received:
June 08 1993
Accepted:
June 08 1993
PubMed:
8375590
Citation
Wolfgang F Graier, Thomas C Wascher, Lydia Lackner, Hermann Toplak, Günter J Krejs, Walter R Kukovetz; Exposure To Elevated D-Glucose Concentrations Modulates Vascular Endothelial Cell Vasodilatory Response. Diabetes 1 October 1993; 42 (10): 1497–1505. https://doi.org/10.2337/diab.42.10.1497
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