Djurić Dragan, Vusanović Ana, Jakovljević Vladimir
Institute of Medical Physiology, School of Medicine, University of Belgrade, Visegradska 26/II, P.O. Box 783, 11000 Belgrade, Serbia.
Mol Cell Biochem. 2007 Jun;300(1-2):177-83. doi: 10.1007/s11010-006-9381-6. Epub 2006 Nov 30.
The aim of this study was to assess the effects of folic acid on coronary flow and oxidative stress markers with or without non-specific inhibition of nitric oxide synthase by L-NAME in isolated rat hearts. The hearts of male Wistar albino rats (n = 12, age 8 weeks, body mass 180-200 g) were retrograde perfused according to the Langendorff technique at gradually increased constant perfusion pressure (40-120 cmH2O). Coronary flow and markers of oxidative stress: nitrite outflow, superoxide anion production, and index of lipid peroxidation (by measuring thiobarbituric acid reactive substances) in coronary effluent were calculated. The experiments were performed during control conditions and in presence of folic acid (100 microM) alone or folic acid (100 microM) plus L-NAME (30 microM). Control values of coronary flow varied in range from 4.37 +/- 0.10 ml/min/g wt at 40 cmH2O to 12.05 +/- 0.42 ml/min/g wt at 120 cmH2O. Nitrite outflow varied from 1.68 +/- 0.17 nmol/min/g wt at 40 cmH2O to 3.56 +/- 0.17 nmol/min/g wt at 120 cmH2O and was parallel with coronary perfusion pressure-coronary flow curve. Folic acid significantly increased coronary flow (40-120 cmH2O, 5.63 +/- 0.10 ml/min/g wt and 15.2 +/- 0.42 ml/min/g wt, respectively) and was accompanied by significant increase in nitrite outflow (2.28 +/- 0.29 nmol/min/g wt at 40 cmH2O to 6.66 +/- 0.50 nmol/min/g wt at 120 cmH2O). In addition, folic acid significantly decreased superoxide anion production especially at upper coronary perfusion pressure values (60% at 120 cmH2O) and increased index of lipid peroxidation (37.16% at 120 cmH2O), respectively. Folic acid plus L-NAME did not change control values of coronary flow significantly. However, folic acid plus L-NAME increased nitrite outflow especially at upper coronary perfusion pressure values (43.05% at 120 cmH2O) and did not change significantly superoxide anion production or index of lipid peroxidation versus control values, respectively. The results clearly showed that on isolated rat hearts at gradually increased constant perfusion pressure, folic acid increased coronary flow, increased nitrite outflow, decreased superoxide anion production, and increased index of lipid peroxidation. These effects were reversed or blocked by L-NAME thus demonstrating mediation or at least participation of NO in the mechanism of the folic acid-induced effects.
本研究旨在评估叶酸对离体大鼠心脏冠状动脉血流及氧化应激标志物的影响，同时观察一氧化氮合酶非特异性抑制剂L - 硝基精氨酸甲酯（L - NAME）存在或不存在时的情况。雄性Wistar白化大鼠（n = 12，8周龄，体重180 - 200 g）的心脏按照Langendorff技术在逐渐升高的恒定灌注压力（40 - 120 cmH₂O）下进行逆行灌注。计算冠状动脉血流以及氧化应激标志物：冠状动脉流出液中的亚硝酸盐流出量、超氧阴离子生成量和脂质过氧化指数（通过测量硫代巴比妥酸反应性物质）。实验在对照条件下进行，以及单独使用叶酸（100 μM）或叶酸（100 μM）加L - NAME（30 μM）的情况下进行。冠状动脉血流的对照值范围为40 cmH₂O时4.37 ± 0.10 ml/min/g体重至120 cmH₂O时12.05 ± 0.42 ml/min/g体重。亚硝酸盐流出量在40 cmH₂O时为1.68 ± 0.17 nmol/min/g体重至120 cmH₂O时为3.56 ± 0.17 nmol/min/g体重，且与冠状动脉灌注压力 - 冠状动脉血流曲线平行。叶酸显著增加冠状动脉血流（40 - 120 cmH₂O时分别为5.63 ± 0.10 ml/min/g体重和15.2 ± 0.42 ml/min/g体重），并伴有亚硝酸盐流出量的显著增加（40 cmH₂O时为2.28 ± 0.29 nmol/min/g体重至120 cmH₂O时为6.66 ± 0.50 nmol/min/g体重）。此外，叶酸显著降低超氧阴离子生成量，尤其是在较高冠状动脉灌注压力值时（120 cmH₂O时降低60%），并增加脂质过氧化指数（120 cmH₂O时增加37.16%）。叶酸加L - NAME未显著改变冠状动脉血流的对照值。然而，叶酸加L - NAME增加了亚硝酸盐流出量，尤其是在较高冠状动脉灌注压力值时（120 cmH₂O时增加43.05%），并且与对照值相比，超氧阴离子生成量或脂质过氧化指数未显著改变。结果清楚地表明，在逐渐升高的恒定灌注压力下，叶酸增加离体大鼠心脏的冠状动脉血流，增加亚硝酸盐流出量，降低超氧阴离子生成量，并增加脂质过氧化指数。这些作用被L - NAME逆转或阻断，从而证明一氧化氮（NO）在叶酸诱导作用机制中起介导作用或至少参与其中。
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