title: Antioxidant treatment alters peripheral vascular dysfunction induced by postnatal glucocorticoid therapy in rats.
abstract: BACKGROUND
  Postnatal glucocorticoid therapy in premature infants diminishes chronic lung disease, but it also increases the risk of hypertension in adulthood. Since glucocorticoid excess leads to overproduction of free radicals and endothelial dysfunction, this study tested the hypothesis that adverse effects on cardiovascular function of postnatal glucocorticoids are secondary to oxidative stress. Therefore, combined postnatal treatment of glucocorticoids with antioxidants may diminish unwanted effects.
  
  
  RESULTS
  Male rat pups received a course of dexamethasone (Dex), or Dex with vitamins C and E (DexCE), on postnatal days 1-6 (P1-6). Controls received vehicle (Ctrl) or vehicle with vitamins (CtrlCE). At P21, femoral vascular reactivity was determined via wire myography. Dex, but not DexCE or CtrlCE, increased mortality relative to Ctrl (81.3 versus 96.9 versus 90.6 versus 100% survival, respectively; P<0.05). Constrictor responses to phenylephrine (PE) and thromboxane were enhanced in Dex relative to Ctrl (84.7+/-4.8 versus 67.5+/-5.7 and 132.7+/-4.9 versus 107.0+/-4.9% Kmax, respectively; P<0.05); effects that were diminished in DexCE (58.3+/-7.5 and 121.1+/-4.3% Kmax, respectively; P<0.05). Endothelium-dependent dilatation was depressed in Dex relative to Ctrl (115.3+/-11.9 versus 216.9+/-18.9, AUC; P<0.05); however, this effect was not restored in DexCE (68.3+/-8.3, AUC). Relative to Ctrl, CtrlCE alone diminished PE-induced constriction (43.4+/-3.7% Kmax) and the endothelium-dependent dilatation (74.7+/-8.7 AUC; P<0.05).
  
  
  CONCLUSIONS
  Treatment of newborn rats with dexamethasone has detrimental effects on survival and peripheral vasoconstrictor function. Coadministration of dexamethasone with antioxidant vitamins improves survival and partially restores vascular dysfunction. Antioxidant vitamins alone affect peripheral vascular function.
authors.affiliation: Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Emilio A
authors.initials: EA
authors.lastname: Herrera
authors.forename: Misha M
authors.initials: MM
authors.lastname: Verkerk
authors.forename: Jan B
authors.initials: JB
authors.lastname: Derks
authors.forename: Dino A
authors.initials: DA
authors.lastname: Giussani
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D003907:Dexamethasone / Q000627:therapeutic use / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005263:Femoral Artery / Q000503:physiopathology; D005938:Glucocorticoids / Q000627:therapeutic use / Q000633:toxicity; D066298:In Vitro Techniques; D008297:Male; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010538:Peritonitis / Q000188:drug therapy / Q000401:mortality; D011188:Potassium / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D005938:Glucocorticoids; D020030:Nitric Oxide Donors; D014810:Vitamin E; D009599:Nitroprusside; D003907:Dexamethasone; D001205:Ascorbic Acid; D011188:Potassium