Jakovljevic V Lj, Canovic P S, Andjelkovic N V, Djuric D M
Department of Physiology, Faculty of Medicine, University of Kragujevac, Svetotazara Markovica 69, P.O. Box 124, 34000 Kragujevac, Serbia.
Acta Physiol Hung. 2006 Dec;93(4):251-61. doi: 10.1556/APhysiol.93.2006.4.1.
The aim of this study was to assess the effects of Ca2+ channel antagonist nimodipine (in concentration which competitive inhibited phosphodiesterase 1--PDE1) on oxidative stress alone or under inhibition of nitric oxide synthase by L-NAME in isolated rat heart. The hearts from male Wistar albino rats (n=18, BM about 200 g, age 8 weeks) were retrograde perfused according to the Langendorff technique at gradually increased constant perfusion pressure conditions (CPP, 40-120 cm H2O). The experiments were performed under control conditions, in the presence of Nimodipine (2 microM) or Nimodipine (2 microM) plus L-NAME (30 microM). Coronary flow (CF) varied in the autoregulatory range from 3.7 +/- 0.4 ml/min/g wt at 50 cm H2O to 4.35 +/- 0.79 at 90 cm H2O. Basal nitrite outflow, index of lipid peroxidation (measured as TBARS release) and superoxide anion release (O2-) (at 60 cm H2O) were 0.64 +/- 0.18 nmol/min/g wt, 0.55 +/- 0.13 micromol/min/g wt and 19.72 +/- 3.70 nmol/min/g wt, respectively. Nimodipine induced significant vasodilation at all values of CPP (from 26% at 40 cm H2O to 36% at 120 cm H2O) accompanied with significant decrease of nitrite outflow (from 59% at 40 cm H2O to 40% at 120 cm H2O), significant increase of TBARS above autoregulatory range (about 40%) and significant increase of O2- release (from 186% at 40 cm H2O to 117% at 120 cm H2O). However, perfusion with L-NAME completely reversed the effects of Nimodipine. Nimodipine-induced flow changes were decreased under L-NAME (from 3% at 40 cm H2O to 11% at 120 cm H2O) without changes in the autoregulatory range, accompanied with significantly increased nitrite outflow (from 69% at 40 cm H2O to 36% at 120 cm H2O) and TBARS release (almost 50%), as well as significantly decreased O2- release (from 50% at 40 cm H2O to 43% at 120 cm H20). Our findings show that effect of nimodipine on coronary flow should be significantly influenced by NO, TBARS and O2- release in isolated rat heart.
本研究的目的是评估钙离子通道拮抗剂尼莫地平（浓度可竞争性抑制磷酸二酯酶1 - PDE1）单独作用或在L - NAME抑制一氧化氮合酶的情况下对离体大鼠心脏氧化应激的影响。雄性Wistar白化大鼠（n = 18，体重约200 g，8周龄）的心脏按照Langendorff技术在逐渐升高的恒定灌注压力条件（CPP，40 - 120 cm H₂O）下进行逆行灌注。实验在对照条件下、尼莫地平（2 microM）存在时或尼莫地平（2 microM）加L - NAME（30 microM）存在时进行。冠状动脉血流量（CF）在自动调节范围内变化，从50 cm H₂O时的3.7±0.4 ml/min/g体重到90 cm H₂O时的4.35±0.79。基础亚硝酸盐流出量、脂质过氧化指标（以TBARS释放量衡量）和超氧阴离子释放量（O₂⁻）（在6 cm H₂O时）分别为0.64±0.18 nmol/min/g体重、0.55±0.13 micromol/min/g体重和19.72±3.70 nmol/min/g体重。尼莫地平在所有CPP值下均引起显著的血管舒张（从40 cm H₂O时的26%到120 cm H₂O时的36%），同时亚硝酸盐流出量显著减少（从40 cm H₂O时的59%到120 cm H₂O时的40%），在自动调节范围以上TBARS显著增加（约40%），O₂⁻释放量显著增加（从40 cm H₂O时的186%到120 cm H₂O时的117%）。然而，用L - NAME灌注完全逆转了尼莫地平的作用。在L - NAME存在下，尼莫地平诱导的血流量变化减少（从40 cm H₂O时的3%到120 cm H₂O时的11%），自动调节范围无变化，同时亚硝酸盐流出量显著增加（从40 cm H₂O时的69%到120 cm H₂O时的36%）和TBARS释放量增加（近50%），以及O₂⁻释放量显著减少（从cm H₂O时的50%到120 cm H₂O时的43%）。我们的研究结果表明，在离体大鼠心脏中，尼莫地平对冠状动脉血流量的影响应受到一氧化氮、TBARS和O₂⁻释放的显著影响。
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