Background: Adrenocorticotropic hormone (ACTH)-induced hypertension in the rat is accompanied by increased oxidative stress. This study examines the enzymatic source of reactive oxygen species in ACTH-hypertension. Methods: Male Sprague-Dawley rats were divided into 10 groups of 10-20 rats per group. The NAD(P)H oxidase inhibitor apocynin (1.5 mmol/L in drinking water) or the xanthine oxidase inhibitor allopurinol (200 mg/kg/day via food) were administered daily. After 4 days, rats were co-administered ACTH (0.2 mg/kg/day) or saline by subcutaneous injection daily for 11 days (prevention study). In a reversal study, ACTH/saline was administered for 13 days and from day 8, apocynin or allopurinol was added for 5 days. Systolic blood pressure (SBP) was measured by the tail-cuff method and oxidative stress using plasma F 2-isoprostane concentrations. Results were expressed as mean ± SEM. Results: ACTH increased SBP (P < .001) but apocynin or allopurinol alone had no effect. Apocynin (but not allopurinol) co-treatment prevented (142 ± 3 ACTH, 120 ± 4 mm Hg apocynin+ACTH, P′<0.001) and reversed ACTH-induced hypertension (133 ± 4 to 118 ± 5 mm Hg, P < .05). Plasma F2-isoprostane concentrations were increased in ACTH-treated rats compared with saline (11.9 ± 1.0 vs 8.2 ± 0.8 nmol/L, P < .01), and apocynin attenuated the ACTH-induced rise in plasma F2-isoprostane concentrations. Serum urate concentrations were undetectable in 75% of rats treated with allopurinol and were not affected by ACTH. Conclusions: Apocynin but not allopurinol prevented and reversed ACTH-induced hypertension in the rat. These results suggest superoxide production through NAD(P)H oxidase plays a role in ACTH-induced hypertension. © 2005 American Journal of Hypertension, Ltd.
Zhang, Y., Chan, M. M. K., Andrews, M. C., Mori, T. A., Croft, K. D., McKenzie, K. U. S., … Whitworth, J. A. (2005). Apocynin but not allopurinol prevents and reverses adrenocorticotropic hormone-induced hypertension in the rat. American Journal of Hypertension, 18(7), 910–916. https://doi.org/10.1016/j.amjhyper.2005.02.017