title: The effect of alpha-lipoic acid on mitochondrial superoxide and glucocorticoid-induced hypertension.
abstract: OBJECTIVE
  To examine the effect of alpha-lipoic acid, an antioxidant with mitochondrial superoxide inhibitory properties, on adrenocorticotrophic hormone- (ACTH-HT) and dexamethasone-induced hypertensions (DEX-HT) in rats and if any antihypertensive effect is mediated via mitochondrial superoxide inhibition.
  
  
  METHODS
  In a prevention study, rats received ground food or alpha-lipoic-acid-laced food (10 mg/rat/day) for 15 nights. Saline, adrenocorticotrophic hormone (ACTH, 0.2 mg/kg/day), or dexamethasone (DEX, 10  μ g/rat/day) was injected subcutaneously from day 5 to day 11. In a reversal study, rats received alpha-lipoic-acid-laced food 4 days after commencement of saline or DEX. Tail-cuff systolic blood pressure (SBP) was measured second daily. Kidney mitochondrial superoxide was examined using (MitoSOX) Red (MitoSOX) via flow cytometry.
  
  
  RESULTS
  SBP was increased by ACTH (P < 0.0005) and DEX (P < 0.0005). Alpha-lipoic acid alone did not alter SBP. With alpha-lipoic acid pretreatment, SBP was increased by ACTH (P' < 0.005) but not by DEX. Alpha-lipoic partially prevented ACTH-HT (P' < 0.0005) and fully prevented DEX-HT (P' < 0.0005) but failed to reverse DEX-HT. ACTH and DEX did not increase MitoSOX signal. In ACTH-hypertensive rats, high-dose alpha-lipoic acid (100 mg/rat/day) did not decrease SBP further but raised MitoSOX signal (P < 0.001), suggesting prooxidant activity.
  
  
  CONCLUSIONS
  Glucocorticoid-induced hypertension in rats is prevented by alpha-lipoic acid via mechanisms other than mitochondrial superoxide reduction.
authors.affiliation: Department of Renal Medicine, St George Hospital, Kogarah, NSW 2217, Australia. s.ong@unsw.edu.au
authors.forename: Sharon L H
authors.initials: SL
authors.lastname: Ong
authors.forename: Harpreet
authors.initials: H
authors.lastname: Vohra
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Matthew
authors.initials: M
authors.lastname: Sutton
authors.forename: Judith A
authors.initials: JA
authors.lastname: Whitworth
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000633:toxicity; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001794:Blood Pressure / Q000502:physiology; D003907:Dexamethasone / Q000633:toxicity; D028441:F2-Isoprostanes / Q000097:blood; D005938:Glucocorticoids / Q000633:toxicity; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D007668:Kidney / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism*; D008063:Thioctic Acid / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D028441:F2-Isoprostanes; D005938:Glucocorticoids; D009566:Nitrates; D009573:Nitrites; D013481:Superoxides; D008063:Thioctic Acid; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone