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 μg/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.