title: The anti-oxidant Tempol reverses and partially prevents adrenocorticotrophic hormone-induced hypertension in the rat.
abstract: OBJECTIVE
  To investigate the effects of the antioxidant Tempol on prevention and reversal of adrenocorticotrophic hormone (ACTH)-induced hypertension in the rat, a model of hypertension characterized by nitric oxide deficiency.
  
  
  METHODS
  Male Sprague-Dawley rats (n = 10 in each group) were treated with either saline or ACTH (0.2 mg/kg per day, s.c.) for 12 days. Tempol (1 mmol/l in drinking water) treatment was started on either day 8 (T8) of ACTH or saline treatment (reversal study), or 4 days prior to ACTH or saline treatment (prevention study). Systolic blood pressure (SBP) was measured using tail-cuff sphygmomanometry. Plasma F2-isoprostanes, a marker of oxidative stress, were measured by gas chromatography-mass spectrometry.
  
  
  RESULTS
  ACTH increased SBP (mean +/- SEM: 119 +/- 5 to 147 +/- 7 mmHg, P < 0.0005) and plasma F2-isoprostane concentration (8.4 +/- 1.2 saline versus 12.9 +/- 1.6 nmol/l ACTH, P < 0.05). Tempol alone did not alter SBP, but administration of Tempol on T8 reversed ACTH-induced hypertension (from 134 +/- 4 T8 to 118 +/- 3 mmHg, P < 0.005). Tempol pre-treatment partially prevented ACTH-induced hypertension (123 +/- 2 mmHg, P' < 0.05). However, Tempol had no effect on F2-isoprostane concentrations at the dose used in this study.
  
  
  CONCLUSIONS
  ACTH-induced hypertension in the rat is associated with increased oxidative stress. Tempol treatment reversed, and pretreatment partially prevented ACTH-induced hypertension, independent of improvement in systemic oxidative stress.
authors.affiliation: High Blood Pressure Research Unit, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ryan
authors.initials: R
authors.lastname: Jang
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Mori
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Croft
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Schyvens
authors.forename: Katja U S
authors.initials: KU
authors.lastname: McKenzie
authors.forename: Judith A
authors.initials: JA
authors.lastname: Whitworth
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D028441:F2-Isoprostanes / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism* / Q000517:prevention & control; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology; D013113:Spin Labels
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D028441:F2-Isoprostanes; D013113:Spin Labels; D009569:Nitric Oxide; D012965:Sodium Chloride; D000324:Adrenocorticotropic Hormone; C001803:tempol