Zhang, YiChan, MatthewAndrews, MilesMori, Trevor ACroft, Kevin DMcKenzie, KatjaSchyvens, ChrisWhitworth, Judith2015-12-130895-7061http://hdl.handle.net/1885/83237Background: 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.Keywords: allopurinol; apocynin; corticotropin; drinking water; isoprostane derivative; oxidoreductase inhibitor; reactive oxygen metabolite; reduced nicotinamide adenine dinucleotide phosphate oxidase; sodium chloride; superoxide; urate; xanthine oxidase inhibitor Adrenocorticotropic hormone; Hypertension; NAD(P)H oxidase; Reactive oxygen species; Xanthine oxidase200510.1016/j.amjhyper.2005.02.0172015-12-12