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.