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Apocynin but not allopurinol prevents and reverses ACTH-induced hypertension in the rat

Zhang, Yi; Chan, Matthew; Andrews, Miles; Mori, Trevor A; Croft, Kevin D; McKenzie, Katja; Schyvens, Chris; Whitworth, Judith

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Background: Adrenocorticotropic hormone (ACTH)-induced hypertension in the rat is accompanied by increased oxidative stress. This study examines the enzymatic source of reactive oxygen species in ACTH-hypertension. Methods: Male Sprague-Dawley rats were divided into 10 groups of 10-20 rats per group. The NAD(P)H oxidase inhibitor apocynin (1.5 mmol/L in drinking water) or the xanthine oxidase inhibitor allopurinol (200 mg/kg/day via food) were administered daily. After 4 days, rats were...[Show more]

dc.contributor.authorZhang, Yi
dc.contributor.authorChan, Matthew
dc.contributor.authorAndrews, Miles
dc.contributor.authorMori, Trevor A
dc.contributor.authorCroft, Kevin D
dc.contributor.authorMcKenzie, Katja
dc.contributor.authorSchyvens, Chris
dc.contributor.authorWhitworth, Judith
dc.date.accessioned2015-12-13T22:58:00Z
dc.identifier.issn0895-7061
dc.identifier.urihttp://hdl.handle.net/1885/83237
dc.description.abstractBackground: Adrenocorticotropic hormone (ACTH)-induced hypertension in the rat is accompanied by increased oxidative stress. This study examines the enzymatic source of reactive oxygen species in ACTH-hypertension. Methods: Male Sprague-Dawley rats were divided into 10 groups of 10-20 rats per group. The NAD(P)H oxidase inhibitor apocynin (1.5 mmol/L in drinking water) or the xanthine oxidase inhibitor allopurinol (200 mg/kg/day via food) were administered daily. After 4 days, rats were co-administered ACTH (0.2 mg/kg/day) or saline by subcutaneous injection daily for 11 days (prevention study). In a reversal study, ACTH/saline was administered for 13 days and from day 8, apocynin or allopurinol was added for 5 days. Systolic blood pressure (SBP) was measured by the tail-cuff method and oxidative stress using plasma F 2-isoprostane concentrations. Results were expressed as mean ± SEM. Results: ACTH increased SBP (P < .001) but apocynin or allopurinol alone had no effect. Apocynin (but not allopurinol) co-treatment prevented (142 ± 3 ACTH, 120 ± 4 mm Hg apocynin+ACTH, P′<0.001) and reversed ACTH-induced hypertension (133 ± 4 to 118 ± 5 mm Hg, P < .05). Plasma F2-isoprostane concentrations were increased in ACTH-treated rats compared with saline (11.9 ± 1.0 vs 8.2 ± 0.8 nmol/L, P < .01), and apocynin attenuated the ACTH-induced rise in plasma F2-isoprostane concentrations. Serum urate concentrations were undetectable in 75% of rats treated with allopurinol and were not affected by ACTH. Conclusions: Apocynin but not allopurinol prevented and reversed ACTH-induced hypertension in the rat. These results suggest superoxide production through NAD(P)H oxidase plays a role in ACTH-induced hypertension.
dc.publisherElsevier
dc.sourceAmerican Journal of Hypertension
dc.subjectKeywords: allopurinol; apocynin; corticotropin; drinking water; isoprostane derivative; oxidoreductase inhibitor; reactive oxygen metabolite; reduced nicotinamide adenine dinucleotide phosphate oxidase; sodium chloride; superoxide; urate; xanthine oxidase inhibitor Adrenocorticotropic hormone; Hypertension; NAD(P)H oxidase; Reactive oxygen species; Xanthine oxidase
dc.titleApocynin but not allopurinol prevents and reverses ACTH-induced hypertension in the rat
dc.typeJournal article
local.description.notesImported from ARIES
local.description.refereedYes
local.identifier.citationvolume18
dc.date.issued2005
local.identifier.absfor110201 - Cardiology (incl. Cardiovascular Diseases)
local.identifier.ariespublicationMigratedxPub11460
local.type.statusPublished Version
local.contributor.affiliationZhang, Yi, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationChan, Matthew, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationAndrews, Miles, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationMori, Trevor A, University of Western Australia
local.contributor.affiliationCroft, Kevin D, University of Western Australia
local.contributor.affiliationMcKenzie, Katja, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationSchyvens, Chris, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationWhitworth, Judith, College of Medicine, Biology and Environment, ANU
local.description.embargo2037-12-31
local.bibliographicCitation.startpage910
local.bibliographicCitation.lastpage916
local.identifier.doi10.1016/j.amjhyper.2005.02.017
dc.date.updated2015-12-12T07:20:21Z
local.identifier.scopusID2-s2.0-22844432344
CollectionsANU Research Publications

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