Verbeuren T J, Bonhomme E, Laubie M, Simonet S
Institut de Recherches Servier, Division of Angiology, Suresnes, France.
J Cardiovasc Pharmacol. 1993 May;21(5):841-5. doi: 10.1097/00005344-199305000-00023.
The aim of our study was to examine the effects of the inhibitor of nitric oxide (NO)-synthase, nitro-L-arginine (L-NNA), in atherosclerotic aortas obtained from cholesterol-fed rabbits. In the atherosclerotic aortas, L-NNA (100 microM) caused endothelium-independent contractions that were not observed in aortas from control rabbits. L-NNA (100 microM) significantly enhanced the contractile responses to norepinephrine and 5-hydroxytryptamine (5-HT) in atherosclerotic aortas with and without endothelium; in control aortas, L-NNA only augmented the response to 5-HT when the endothelium was present. The concentration-dependent increases in the norepinephrine-induced contractions caused by L-NNA (1 to 100 microM) could be reversed by L-arginine (1 mM) both in atherosclerotic aortas with and without endothelium. L-NMMA also evoked concentration-dependent augmentations of the norepinephrine-induced contraction; the effect of L-NMMA was equipotent to that of L-NNA. Finally, L-NNA (100 microM) prevented the paradoxical endothelium-independent contraction to hypoxia in atherosclerotic aortas. These data strongly suggest that nonendothelial NO synthase has been induced in the aortas of the hyperlipidemic rabbit.
我们研究的目的是检测一氧化氮（NO）合酶抑制剂硝基-L-精氨酸（L-NNA）对从喂食胆固醇的兔子获得的动脉粥样硬化主动脉的影响。在动脉粥样硬化主动脉中，L-NNA（100微摩尔）引起了非内皮依赖性收缩，而在对照兔子的主动脉中未观察到这种收缩。L-NNA（100微摩尔）显著增强了有内皮和无内皮的动脉粥样硬化主动脉对去甲肾上腺素和5-羟色胺（5-HT）的收缩反应；在对照主动脉中，L-NNA仅在有内皮时增强对5-HT的反应。L-NNA（1至100微摩尔）引起的去甲肾上腺素诱导的收缩的浓度依赖性增加可被L-精氨酸（1毫摩尔）在有内皮和无内皮的动脉粥样硬化主动脉中逆转。L-NMMA也引起去甲肾上腺素诱导的收缩的浓度依赖性增强；L-NMMA的作用与L-NNA相当。最后，L-NNA（100微摩尔）阻止了动脉粥样硬化主动脉中对缺氧的反常非内皮依赖性收缩。这些数据强烈表明高脂血症兔子的主动脉中诱导了非内皮型NO合酶。
