Document Detail


Apocynin but not L-arginine prevents and reverses dexamethasone-induced hypertension in the rat.
MedLine Citation:
PMID:  16580579     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Dexamethasone (Dex)-hypertension in rats is associated with increased oxidative stress. We investigated effects of the NAD(P)H oxidase inhibitor apocynin and the nitric oxide (NO) precursor L-arginine on Dex-hypertension to determine the relative roles of NAD(P)H oxidase and uncoupling in the reactive oxygen species (ROS) generation and hypertension. METHODS: Male Sprague-Dawley rats (n = 10/group) received Dex (20 microg/kg/day subcutaneously) or saline (vehicle) for 14 days. In a prevention study, rats received 4 days of apocynin treatement (1.5 mmol/L in drinking water) followed by Dex/saline for 12 days. In reversal studies, apocynin or L-arginine was given from day 8 to 14. Systolic blood pressure (SBP) was measured by tail cuff, and thymus weight was used as a marker of glucocorticoid activity. RESULTS: Administration of Dex increased SBP (104 +/- 3 to 122 +/- 3 mm Hg, P < .01, mean +/- SEM) and decreased thymus and body weight (P' < .05). Apocynin alone had no effect on SBP, BW, or thymus weight. Apocynin prevented (122 +/- 4 Dex, 111 +/- 3 mm Hg Apocynin+Dex, P' < .05) and reversed Dex-hypertension (130 +/- 4 to 116 +/- 4 mm Hg, P < .01). L-arginine did not reverse Dex-hypertension. CONCLUSIONS: In male SD rats, apocynin but not l-arginine prevented and reversed Dex-hypertension, suggesting that NAD(P)H oxidase-mediated superoxide production but not endothelial nitric oxide synthase uncoupling is important in Dex-hypertension.
Authors:
Lexian Hu; Yi Zhang; Pek S Lim; Yuchun Miao; Chrismin Tan; Katja U S McKenzie; Christopher G Schyvens; Judith A Whitworth
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  American journal of hypertension     Volume:  19     ISSN:  0895-7061     ISO Abbreviation:  Am. J. Hypertens.     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-04-03     Completed Date:  2006-08-22     Revised Date:  2009-02-24    
Medline Journal Info:
Nlm Unique ID:  8803676     Medline TA:  Am J Hypertens     Country:  United States    
Other Details:
Languages:  eng     Pagination:  413-8     Citation Subset:  IM    
Affiliation:
High Blood Pressure Research Unit, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia.
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MeSH Terms
Descriptor/Qualifier:
Acetophenones / pharmacology*
Animals
Arginine / deficiency,  pharmacology*
Blood Pressure / drug effects
Dexamethasone / adverse effects*
Endothelium, Vascular / metabolism
Enzyme Inhibitors / pharmacology*
Hypertension / chemically induced*,  physiopathology,  prevention & control*
Male
NADPH Oxidase / antagonists & inhibitors,  physiology
Nitric Oxide Synthase / metabolism
Nitric Oxide Synthase Type III / metabolism
Organ Size
Oxidative Stress / drug effects,  physiology
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species / metabolism
Superoxides / metabolism
Thymus Gland / pathology
Chemical
Reg. No./Substance:
0/Acetophenones; 0/Enzyme Inhibitors; 0/Reactive Oxygen Species; 11062-77-4/Superoxides; 498-02-2/acetovanillone; 50-02-2/Dexamethasone; 74-79-3/Arginine; EC 1.14.13.39/NOS3 protein, human; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.6.3.1/NADPH Oxidase

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