Nisoldipine increases the bioavailability of endothelial NO
Nisoldipine increases the bioavailability of endothelial NO
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DOI：
10.1007/s002100100429
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发表时间：
2001-08-01
影响因子：
3.6
通讯作者：
Klaus, W
中科院分区：
文献类型：
--
作者：
Berkels, R;Roesen, R;Klaus, W
不同的观察结果表明，二氢吡啶类钙拮抗剂会改变内皮一氧化氮的释放。因此，首先我们研究了尼索地平（一种可能对冠状动脉有选择性的二氢吡啶类钙拮抗剂）诱导的血管舒张是否部分是由于猪冠状动脉内皮释放一氧化氮所致。其次，我们直接测量尼索地平是否会增加兔主动脉一氧化氮的释放，以及尼索地平对映体（Bay R 1223，Bay R 1224）是否会增加大鼠主动脉一氧化氮的释放。第三，我们确定尼索地平是否对具有完整内皮的猪主动脉段具有抗氧化特性。用N - 硝基 - L - 精氨酸阻断内皮一氧化氮合酶会导致舒张曲线显著向更高浓度偏移。相应地，尼索地平从天然内皮诱导了一氧化氮的浓度依赖性释放（直接电化学检测），这种释放在治疗水平（1纳摩尔/升尼索地平/6.5 ± 1.2纳摩尔/升一氧化氮）就已开始。为了评估这种效应是否是由于对一氧化氮的抗氧化保护，我们研究了尼索地平对高血糖（30毫摩尔/升，20分钟）诱导的猪冠状动脉血管内皮活性氧释放的影响。尼索地平浓度依赖性地减少活性氧释放（>50%；10微摩尔/升）。此外，在尼索地平（3微摩尔/升）存在的情况下，高血糖显著降低的卡巴胆碱诱导的一氧化氮释放（兔主动脉）完全恢复。我们得出结论，尼索地平增加了一氧化氮的生物利用度，这可能导致内皮功能改善。
Different observations suggest that dihydropyridine calcium antagonists alter endothelial NO release. Therefore, in a first step we investigated whether part of the nisoldipine (a dihydropyridine calcium antagonist with a possible selectivity for coronaries)-induced vasorelaxation was due to an NO release from the endothelium in porcine coronary arteries. Secondly, we directly measured whether nisoldipine increased NO release from rabbit aorta or the nisoldipine enantiomers (Bay R 1223, Bay R 1224) from rat aorta. Thirdly, we determined whether nisoldipine exerted antioxidative properties in segments of porcine aorta with intact endothelium.Blocking endothelial NO synthase with N-nitro-L-arginine resulted in a significant shift of the relaxation curve to higher concentrations. Accordingly, nisoldipine induced a concentration-dependent release of NO (direct electrochemical detection) from native endothelium which already started at a therapeutical level (1 nmol/l nisoldipine/6.5 +/-1.2 nmol/l NO). To evaluate whether this effect was due to an antioxidative protection of NO, we examined the influence of nisoldipine on a hyperglycemia (30 mmol/l, 20 min)-induced reactive oxygen species release of vascular endothelium from porcine coronary arteries. Nisoldipine concentration-dependently reduced the reactive oxygen species release (>50%; 10 Lmol/l). Moreover, a carbachol-induced NO release (rabbit aorta) which was significantly diminished by hyperglycemia was completely restored in the presence of nisoldipine (3 mu mol/l). We conclude that nisoldipine increases the NO bioavailability which may result in an ameliorated endothelial function.