Apocynin but Not Allopurinol Prevents and Reverses Adrenocorticotropic Hormone-Induced Hypertension in the Rat

• Published in: American journal of hypertension 2005-07, Vol.18 (7), p.910-916
• Main Authors: Zhang, Yi, Chan, Matthew M.K., Andrews, Miles C., Mori, Trevor A., Croft, Kevin D., McKenzie, Katja U.S., Schyvens, Christopher G., Whitworth, Judith A.
• Format: Article
• Language: English
• Subjects: Acetophenones - therapeutic use; Adrenocorticotropic Hormone; Allopurinol - therapeutic use; Animals; Antihypertensive Agents - therapeutic use; Antioxidants - therapeutic use; Aorta, Thoracic - drug effects; Aorta, Thoracic - metabolism; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Body Weight - drug effects; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Enzyme Inhibitors - therapeutic use; Experimental diseases; hypertension; Hypertension - chemically induced; Hypertension - drug therapy; Isoprostanes - blood; Male; Medical sciences; NAD(P)H oxidase; NADPH Oxidases - antagonists & inhibitors; NADPH Oxidases - metabolism; Organ Size - drug effects; Oxidative Stress - drug effects; Rats; Rats, Sprague-Dawley; reactive oxygen species; Reactive Oxygen Species - metabolism; Superoxides - metabolism; Thymus Gland - anatomy & histology; Thymus Gland - drug effects; Uric Acid - urine; xanthine oxidase; Xanthine Oxidase - antagonists & inhibitors; Xanthine Oxidase - metabolism
• ISSN: 0895-7061; 1879-1905; 1941-7225
• DOI: 10.1016/j.amjhyper.2005.02.017

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. 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 F2-isoprostane concentrations. Results were expressed as mean ± SEM. 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′