Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
PLoS One. 2010 Feb 17;5(2):e9250. doi: 10.1371/journal.pone.0009250.
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.
METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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.
早产儿出生后接受糖皮质激素治疗可减轻慢性肺部疾病，但会增加成年后患高血压的风险。由于糖皮质激素过多会导致自由基产生过多和内皮功能障碍，因此本研究检测了出生后糖皮质激素的心血管不良影响继发于氧化应激的假说。因此，联合应用出生后糖皮质激素和抗氧化剂治疗可能会减少不良反应。
方法/主要发现：雄性幼鼠在出生后第 1-6 天（P1-6）接受地塞米松（Dex）或地塞米松加维生素 C 和 E（DexCE）治疗。对照组接受载体（Ctrl）或载体加维生素（CtrlCE）。在 P21 时，通过电测线描记术测定股血管反应性。与 Ctrl 相比，Dex 但不是 DexCE 或 CtrlCE 增加死亡率（分别为 81.3%±4.8%、67.5%±5.7%和 107.0%±4.9%，分别为 96.9%、90.6%和 100%的存活率；P<0.05）。与 Ctrl 相比，Dex 对苯肾上腺素（PE）和血栓素的收缩反应增强（分别为 84.7%±4.8%、132.7%±4.9%和 67.5%±5.7%，Kmax；P<0.05），而在 DexCE 中减弱（分别为 58.3%±7.5%和 121.1%±4.3%，Kmax；P<0.05）。与 Ctrl 相比，Dex 相对的内皮依赖性扩张减弱（115.3%±11.9%与 216.9%±18.9%，AUC；P<0.05）；然而，在 DexCE 中并未恢复（68.3%±8.3%，AUC）。与 Ctrl 相比，仅用 CtrlCE 即可减弱 PE 诱导的收缩（43.4%±3.7%，Kmax）和内皮依赖性扩张（74.7%±8.7%，AUC；P<0.05）。
结论/意义：用地塞米松治疗新生大鼠会对生存和外周血管收缩功能产生有害影响。地塞米松与抗氧化维生素联合应用可提高生存率并部分恢复血管功能障碍。单独使用抗氧化维生素会影响外周血管功能。
