Tumour necrosis factor-α (TNFα) is a mediator of reactive oxygen species, which are implicated in endothelial dysfunction and atherosclerosis. Type II diabetes is associated with endothelial dysfunction and elevated circulating TNFα. We hypothesized that reducing serum levels of TNFα, using pentoxifylline, would improve endothelial function. Thirteen subjects [age 58±2 (S.E.M.) years] with Type II diabetes (disease duration 74±13months) undertook a randomized, crossover study of 8weeks pentoxifylline and 8weeks placebo. Endothelium-dependent and-independent vasodilation in resistance arteries was assessed via bilateral forearm venous occlusion plethysmography during intra-brachial infusions of acetylcholine (ACh), sodium nitroprusside (SNP) and NG-monomethyl-l-arginine (l-NMMA). High-resolution ultrasound of the brachial artery in response to ischaemia was used to determine endothelium-dependent conduit vessel flow-mediated dilation (FMD), and endothelium-independent conduit function was assessed by sublingual administration of glyceryl trinitrate (GTN). Serum concentrations of TNFα were also determined. Pentoxifylline lowered serum TNFα from 4.1±0.7 to 2.9±0.6 pg˙ml-1 (P = 0.001). Forearm blood flow (FBF) responses at each dose of ACh did not differ with treatment (P = 0.4). Similarly, FBF responses to SNP (P = 0.8) and l-NMMA (P = 0.2) did not differ. There was also no significant difference in brachial artery diameter during FMD (P = 0.2) or GTN administration (P = 0.06). Despite lowering serum TNFα concentration, pentoxifylline at a dose of 400mg three times a day for 8weeks did not improve vascular function in either conduit or resistance vessels in this group of Type II diabetic subjects.
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Research Article|
July 17 2002
Effect of lowering tumour necrosis factor-α on vascular endothelial function in Type II diabetes
William BILSBOROUGH;
*Department of Cardiothoracic Surgery, Royal Perth Hospital, GPO Box X2213, Perth, WA 6847, Australia
†Cardiac Transplant Unit, Royal Perth Hospital, GPO Box X2213, Perth, WA 6847, Australia
‡The West Australian Institute for Medical Research, B-Block, Queen Elizabeth II Medical Centre, Verdun Street, Nedlands, WA 6008, Australia
Correspondence: Dr W. Bilsborough, Cardiac Transplant Unit, Royal Perth Hospital, GPO Box X2213, Perth, WA 6847, Australia (e-mail [email protected]).
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Gerard O'DRISCOLL;
Gerard O'DRISCOLL
†Cardiac Transplant Unit, Royal Perth Hospital, GPO Box X2213, Perth, WA 6847, Australia
‡The West Australian Institute for Medical Research, B-Block, Queen Elizabeth II Medical Centre, Verdun Street, Nedlands, WA 6008, Australia
§Department of Human Movement and Exercise Science, The University of Western Australia, 35 Stirling Highway, Nedlands, WA 6009, Australia
∥Department of Cardiology, Royal Perth Hospital, GPO Box X2213, Perth, WA 6847, Australia
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Kim STANTON;
Kim STANTON
¶Endocrinology and Diabetic Unit, Royal Perth Hospital, Royal Perth Hospital, GPO Box X2213, Perth, WA 6847, Australia
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Rukshen WEERASOORIYA;
Rukshen WEERASOORIYA
∥Department of Cardiology, Royal Perth Hospital, GPO Box X2213, Perth, WA 6847, Australia
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Lawrence DEMBO;
Lawrence DEMBO
†Cardiac Transplant Unit, Royal Perth Hospital, GPO Box X2213, Perth, WA 6847, Australia
∥Department of Cardiology, Royal Perth Hospital, GPO Box X2213, Perth, WA 6847, Australia
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Roger TAYLOR;
Roger TAYLOR
‡The West Australian Institute for Medical Research, B-Block, Queen Elizabeth II Medical Centre, Verdun Street, Nedlands, WA 6008, Australia
∥Department of Cardiology, Royal Perth Hospital, GPO Box X2213, Perth, WA 6847, Australia
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Daniel GREEN
Daniel GREEN
†Cardiac Transplant Unit, Royal Perth Hospital, GPO Box X2213, Perth, WA 6847, Australia
‡The West Australian Institute for Medical Research, B-Block, Queen Elizabeth II Medical Centre, Verdun Street, Nedlands, WA 6008, Australia
§Department of Human Movement and Exercise Science, The University of Western Australia, 35 Stirling Highway, Nedlands, WA 6009, Australia
∥Department of Cardiology, Royal Perth Hospital, GPO Box X2213, Perth, WA 6847, Australia
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Publisher: Portland Press Ltd
Received:
December 10 2001
Revision Received:
March 11 2002
Accepted:
April 23 2002
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2002
2002
Clin Sci (Lond) (2002) 103 (2): 163–169.
Article history
Received:
December 10 2001
Revision Received:
March 11 2002
Accepted:
April 23 2002
Citation
William BILSBOROUGH, Gerard O'DRISCOLL, Kim STANTON, Rukshen WEERASOORIYA, Lawrence DEMBO, Roger TAYLOR, Daniel GREEN; Effect of lowering tumour necrosis factor-α on vascular endothelial function in Type II diabetes. Clin Sci (Lond) 1 August 2002; 103 (2): 163–169. doi: https://doi.org/10.1042/cs1030163
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