Differential effects of glucose on agonist-induced relaxations in human mesenteric and subcutaneous arteries

MacKenzie, A., Cooper, E.J. and Dowell, F.J. (2008) Differential effects of glucose on agonist-induced relaxations in human mesenteric and subcutaneous arteries. British Journal of Pharmacology, 153(3), pp. 480-487. (doi: 10.1038/sj.bjp.0707592)

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Background and purpose: Acute periods of hyperglycaemia are strongly associated with vascular disorder, yet the specific effects of high glucose on human blood vessel function are not fully understood. In this study we (1) characterized the endothelial-dependent relaxation of two similarly sized but anatomically distinct human arteries to two different agonists and (2) determined how these responses are modified by acute exposure to high glucose. Experimental approach: Ring segments of human mesenteric and subcutaneous arteries were mounted in a wire myograph. Relaxations to acetylcholine and bradykinin were determined in a control (5 mM) and high glucose (20 mM) environment over a 2 and 6 h incubation period. Key results: Bradykinin-induced relaxation in both sets of vessels was mediated entirely by EDHF whilst that generated by acetylcholine, though principally generated by EDHF, also had contribution from prostacyclin and possibly nitric oxide in mesenteric and subcutaneous vessels, respectively. A 2-h incubation of high glucose impaired bradykinin-induced relaxation of subcutaneous vessels whilst, in contrast, the relaxation generated by bradykinin in mesenteric vessels was enhanced at the same time point. High glucose significantly augmented the relaxation generated by acetylcholine in mesenteric and subcutaneous vessels at a 2 and 6 h incubation point, respectively. Conclusions and implications: Short periods of high glucose exert a variable influence on endothelial function in human isolated blood vessels that is dependent on factors of time, agonist-used and vessel studied. This has implications for how we view the effects of acute hyperglycaemia found in patients with diabetes mellitus as well as other conditions.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Dowell, Dr Fiona and Cooper, Dr Emma
Authors: MacKenzie, A., Cooper, E.J., and Dowell, F.J.
College/School:College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:British Journal of Pharmacology
Published Online:29 January 2009

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