Research Paper
Subject Category: Cardiovascular and pulmonary pharmacology
British Journal of Pharmacology (2008) 153, 480–487; doi:10.1038/sj.bjp.0707592; published online 26 November 2007
Differential effects of glucose on agonist-induced relaxations in human mesenteric and subcutaneous arteries
A MacKenzie1, E J Cooper2 and F J Dowell2
- 1School of Engineering and Science, University of Paisley, Hamilton Campus, Hamilton, Lanarkshire, UK
- 2Institute of Comparative Medicine, University of Glasgow Veterinary School, University of Glasgow, Glasgow, Scotland, UK
Correspondence: Dr FJ Dowell, Institute of Comparative Medicine, University of Glasgow Veterinary School, University of Glasgow, Bearsden Road, Glasgow, G61 1QH, Scotland, UK. E-mail: F.Dowell@vet.gla.ac.uk
Received 5 September 2007; Revised 15 October 2007; Accepted 17 October 2007; Published online 26 November 2007.
Abstract
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.
Keywords:
glucose, human arteries, endothelium, EDHF, nitric oxide, vasodilatation
Abbreviations:
EDHF, endothelium-derived hyperpolarizing factor; GTN, glyceryl trinitrate; L-NAME, NG-nitro-L-arginine methyl ester; NO, nitric oxide
