Apocynin but not allopurinol prevents and reverses adrenocorticotropic hormone-induced hypertension in the rat

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 turn Hg apocynin+ACTH, P'< 0.001) and reversed ACTH-induced hypertension (133 +/- 4 to 118 +/- 5 mmHg, P <.05). Plasma F-2-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 F-2-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.