Aspirin Prevents and Partially Reverses Adrenocorticotropic Hormone-Induced Hypertension in the Rat

Background: Glucocorticoid-induced hypertension is associated with increased oxidative stress. The aim of the present study was to investigate the effects of aspirin, a potent antioxidant, on adrenocorticotropic hormone (ACTH) and dexamethasone (Dex)-induced hypertension. Methods: Male Sprague-Dawley (SD) rats were treated with saline, ACTH (0.2 mg/kg/d subcutaneously) or Dex (10 μg/rat/d subcutaneously). Aspirin (100 mg/kg/d in drinking water) was given 4 days before and during glucocorticoid-treatment (prevention studies). In reversal studies, saline, ACTH, or Dex was administered for 13 days and at day 8 (T8), rats were co-administered aspirin for 5 days. Systolic blood pressure (BP) was measured by the tail-cuff method. Thymus wet weight was measured as a marker of glucocorticoid activity and lucigenin-enhanced chemiluminescence as a marker of aortic superoxide production. Results: Saline or aspirin alone did not change systolic BP. Systolic BP was increased by ACTH (mean ± SEM; from 99 ± 2 to 133 ± 4 mm Hg, n = 10, P < .001) and Dex (from 102 ± 3 to 125 ± 5 mm Hg, n = 10, P < .001). Aspirin prevented the development of hypertension caused by ACTH (P′ < .01) and tended to prevent Dex-induced hypertension (P′ = .07). ACTH- but not Dex-induced hypertension was partially reversed by aspirin. Both ACTH and Dex decreased thymus weight. Aspirin had no effect on thymus weight. ACTH tended to increase lucigenin-enhanced chemiluminescence (P′ = .07). Aspirin had no effect on this marker of tissue superoxide production. Conclusions: Aspirin prevented and partially reversed ACTH-induced hypertension in the SD rats.