Apocynin but not L-arginine prevents and reverses dexamethasone-induced hypertension in the rat

Lexian Hu, Yi Zhang, Pek S Lim, Yuchun Miao, Chrismin Tan, Katja U S McKenzie, Christopher G Schyvens, Judith A Whitworth

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)413-8
Number of pages6
JournalAmerican Journal of Hypertension
Volume19
Issue number4
DOIs
Publication statusPublished - 2006
Externally publishedYes

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Dexamethasone
Arginine
Hypertension
Blood Pressure
NADPH Oxidase
Thymus Gland
acetovanillone
Weights and Measures
Nitric Oxide Synthase Type III
Superoxides
Drinking Water
Glucocorticoids
Sprague Dawley Rats
Tail
Reactive Oxygen Species
Nitric Oxide
Oxidative Stress
Body Weight

Cite this

Hu, Lexian ; Zhang, Yi ; Lim, Pek S ; Miao, Yuchun ; Tan, Chrismin ; McKenzie, Katja U S ; Schyvens, Christopher G ; Whitworth, Judith A. / Apocynin but not L-arginine prevents and reverses dexamethasone-induced hypertension in the rat. In: American Journal of Hypertension. 2006 ; Vol. 19, No. 4. pp. 413-8.
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title = "Apocynin but not L-arginine prevents and reverses dexamethasone-induced hypertension in the rat",
abstract = "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.",
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author = "Lexian Hu and Yi Zhang and Lim, {Pek S} and Yuchun Miao and Chrismin Tan and McKenzie, {Katja U S} and Schyvens, {Christopher G} and Whitworth, {Judith A}",
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Apocynin but not L-arginine prevents and reverses dexamethasone-induced hypertension in the rat. / Hu, Lexian; Zhang, Yi; Lim, Pek S; Miao, Yuchun; Tan, Chrismin; McKenzie, Katja U S; Schyvens, Christopher G; Whitworth, Judith A.

In: American Journal of Hypertension, Vol. 19, No. 4, 2006, p. 413-8.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Apocynin but not L-arginine prevents and reverses dexamethasone-induced hypertension in the rat

AU - Hu, Lexian

AU - Zhang, Yi

AU - Lim, Pek S

AU - Miao, Yuchun

AU - Tan, Chrismin

AU - McKenzie, Katja U S

AU - Schyvens, Christopher G

AU - Whitworth, Judith A

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

KW - Acetophenones/pharmacology

KW - Animals

KW - Arginine/deficiency

KW - Blood Pressure/drug effects

KW - Dexamethasone/adverse effects

KW - Endothelium, Vascular/metabolism

KW - Enzyme Inhibitors/pharmacology

KW - Hypertension/chemically induced

KW - Male

KW - NADPH Oxidases/antagonists & inhibitors

KW - Nitric Oxide Synthase/metabolism

KW - Nitric Oxide Synthase Type III/metabolism

KW - Organ Size

KW - Oxidative Stress/drug effects

KW - Rats

KW - Rats, Sprague-Dawley

KW - Reactive Oxygen Species/metabolism

KW - Superoxides/metabolism

KW - Thymus Gland/pathology

U2 - 10.1016/j.amjhyper.2005.09.023

DO - 10.1016/j.amjhyper.2005.09.023

M3 - Article

VL - 19

SP - 413

EP - 418

JO - American Journal of Hypertension

JF - American Journal of Hypertension

SN - 0895-7061

IS - 4

ER -