Apocynin but not L-arginine prevents and reverses dexamethasone-induced hypertension in the rat.
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.
High Blood Pressure Research Unit, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia.
Lexian
L
Hu
Yi
Y
Zhang
Pek S
PS
Lim
Yuchun
Y
Miao
Chrismin
C
Tan
Katja U S
KU
McKenzie
Christopher G
CG
Schyvens
Judith A
JA
Whitworth
D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000172:deficiency / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003907:Dexamethasone / Q000009:adverse effects*; D004730:Endothelium, Vascular / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009929:Organ Size; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013950:Thymus Gland / Q000473:pathology
D000098:Acetophenones; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D013481:Superoxides; D003907:Dexamethasone; D001120:Arginine; C056165:acetovanillone; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases