Type 1 diabetes and hypercholesterolaemia reveal the contribution of endothelium-derived hyperpolarizing factor to endothelium-dependent relaxation of the rat aorta

Malakul, W, Thirawarapan, S, Suritayavat, W and Woodman, O 2008, 'Type 1 diabetes and hypercholesterolaemia reveal the contribution of endothelium-derived hyperpolarizing factor to endothelium-dependent relaxation of the rat aorta', Clinical and Experimental Pharmacology and Physiology, vol. 35, no. 2, pp. 192-200.


Document type: Journal Article
Collection: Journal Articles

Title Type 1 diabetes and hypercholesterolaemia reveal the contribution of endothelium-derived hyperpolarizing factor to endothelium-dependent relaxation of the rat aorta
Author(s) Malakul, W
Thirawarapan, S
Suritayavat, W
Woodman, O
Year 2008
Journal name Clinical and Experimental Pharmacology and Physiology
Volume number 35
Issue number 2
Start page 192
End page 200
Total pages 9
Publisher Wiley-Blackwell Publishing Asia
Abstract 1. The present study evaluated the effect of diabetes, hypercholesterolaemia and their combination on the contribution of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) to relaxation of rat isolated aortic rings and the potential contribution of oxidant stress to the disturbance of endothelial function. 2. Thoracic aortic rings from control, diabetic, hypercholesterolaemic and diabetic plus hypercholesterolaemic rats were suspended in organ baths for tension recording. Generation of superoxide by the aorta was measured using lucigenin-enhanced chemiluminescence. 3. The maximal response to acetylcholine (ACh) was significantly reduced in diabetic or hypercholesterolaemic rats compared with control rats. In rats with diabetes plus hypercholesterolaemia, both the sensitivity and maximal response to ACh was impaired. In control rats, the response to ACh was abolished by the NO synthase inhibitor NG-nitro-l-arginine (l-NNA) or inhibition of soluble guanylate cyclase with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). In contrast, in rats with diabetes, hypercholesterolaemia or both, relaxation to ACh was resistant to inhibition by l-NNA or ODQ, but abolished by additional inhibition of KCa channels with charybdotoxin plus apamin. 4. The generation of superoxide was not significantly enhanced in aortic rings from either diabetic or hypercholesterolaemic rats, but was significantly increased in aortic rings from rats with diabetes plus hypercholesterolaemia. 5. These results suggest that when diabetes and hypercholesterolaemia impair endothelium-dependent relaxation, due to a diminished contribution from NO, a compensatory contribution of EDHF to endothelium-dependent relaxation of the aorta is revealed. The attenuation of NO-mediated relaxation, at least in the presence of both diabetes and hypercholesterolaemia, is associated with enhanced superoxide generation.
Subject Basic Pharmacology
Keyword(s) diabetes
endothelium-dependent relaxation
endothelium-derived hyperpolarising factor
hypercholesterolaemia
superoxide anion
DOI - identifier 10.1111/j.1440-1681.2007.04811.x
Copyright notice © 2007 The Authors.
ISSN 0305-1870
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