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 mug/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.
Zhang
Yi
Y
The High Blood Pressure Research Unit, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia.
Miao
Yuchun
Y
Whitworth
Judith A
JA
D000324:Adrenocorticotropic Hormone; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003907:Dexamethasone; D004791:Enzyme Inhibitors / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control*; D008297:Male; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D009929:Organ Size / Q000187:drug effects; D016877:Oxidants / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism; D013950:Thymus Gland / Q000187:drug effects / Q000254:growth & development
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D016877:Oxidants; D013481:Superoxides; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D019255:NADPH Oxidases; D001241:Aspirin