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Selective inhibition of NADPH oxidase reverses the over contraction of diabetic rat aorta
Biosciences, School of Life and Medical Sciences, University of Hertfordshire, College, United Kingdom.
Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
Biosciences, School of Life and Medical Sciences, University of Hertfordshire, College, United Kingdom.
Biosciences, School of Life and Medical Sciences, University of Hertfordshire, College, United Kingdom.
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2014 (English)In: Redox Biology, ISSN 2213-2317, Vol. 2, no 1, 61-64 p.Article in journal (Refereed) Published
Abstract [en]

Abnormal vascular responsiveness in diabetes has been attributed to a number of changes in contractile pathways, affected in part by the overproduction of reactive oxygen species (ROS). It has been reported that NADPH oxidase (NOX) is increased in diabetic (streptozotocin treated; STZ) rat arteries; however the pharmacological agents used to inhibit NOX activity are known to be unsuitable for in vitro studies and have a high level of non-selectivity. Here we have used the highly selective NOX inhibitor VAS2870 in diabetic rat aorta and compared its effects with apocynin, SOD, and allopurinol on phenylephrine and U46619 induced contraction. Male Wistar rats were injected intraperitoneally with 65mg/kg STZ and development of diabetes was confirmed by testing blood glucose levels. Rats were killed by CO2 asphyxiation, and the thoracic aorta removed and mounted in an organ bath under a tension of 1g. Diabetic rat aortas exhibit a greatly increased response to phenylephrine, which was reduced to a level consistent with control rat aorta by 10-5M VAS2870 and 150U/ml SOD. Incubation with VAS2870 led to an increase in normal rat aorta contraction, but led to a significant reduction in phenylephrine and U46619 induced tone in diabetic rat aorta, which indicates that ROS in diabetic rats directly contributes to these contractile responses. Apocynin and allopurinol had no effect on contraction in diabetic or normal rat aorta. This data is the first to show that selective inhibition of NOX reduces diabetic arterial contraction in direct comparison with inhibition of other known contributors of ROS.

Place, publisher, year, edition, pages
Elsevier, 2014. Vol. 2, no 1, 61-64 p.
Keyword [en]
Aorta; Apocynin; NADPH oxidase (NOX); Reactive oxygen species (ROS); Streptozotocin (STZ); VAS2870
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:liu:diva-109961DOI: 10.1016/j.redox.2013.12.002ISI: 000350769600009Scopus ID: 2-s2.0-84891455814OAI: oai:DiVA.org:liu-109961DiVA: diva2:748216
Available from: 2014-09-18 Created: 2014-08-29 Last updated: 2015-06-01

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CiteExportLink to record
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Citation style
  • apa
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