Aldasoro M, Martínez C, Vila J M, Medina P, Lluch S
Departamento de Fisiología, Universidad de Valencia, Spain.
J Cereb Blood Flow Metab. 1996 Jul;16(4):623-8. doi: 10.1097/00004647-199607000-00012.
The present study was designed to investigate the influence of the endothelium and that of the L-arginine pathway on the contractile responses of isolated human cerebral arteries to electrical field stimulation (EFS) and norepinephrine. Rings of human middle cerebral artery were obtained during autopsy of 19 patients who had died 3-8 h before. EFS (1-8 Hz) induced frequency-dependent contractions that were abolished by tetrodotoxin, prazosin, and guanethidine (all at 10(-6) M). The increases in tension were of greater magnitude in arteries denuded of endothelium. N(G)-monomethyl L-arginine (L-NMMA 10(-4) M) potentiated the contractile response to EFS in artery rings with endothelium but did not influence responses of endothelium-denuded arteries. L-arginine (10(-4) M) reversed the potentiating effects of L-NMMA on EFS-induced contractions. Norepinephrine induced concentration-dependent contractions, which were similar in arteries with and without endothelium or in arteries treated with L-NMMA. Indomethacin (3 x 10(-6) M) had no significant effect on the contractile response to EFS or on the inhibition by L-NMMA of acetylcholine-induced relaxation. These results suggest that the contractile response of human cerebral arteries to EFS is modulated by nitric oxide mainly derived from endothelial cells; although adrenergic nerves appear to be responsible for the contraction, the transmitter involved in the release of nitric oxide does not appear to be norepinephrine. The effects of L-NMMA in this preparation appear to be due to inhibition of nitric oxide formation rather than caused by cyclooxygenase activation.
本研究旨在探讨内皮细胞和L-精氨酸途径对离体人脑动脉对电场刺激（EFS）和去甲肾上腺素收缩反应的影响。从19例死亡3 - 8小时的患者尸检中获取大脑中动脉环。EFS（1 - 8Hz）诱导频率依赖性收缩，这种收缩被河豚毒素、哌唑嗪和胍乙啶（均为10^(-6)M）消除。在内皮剥脱的动脉中，张力增加的幅度更大。N(G)-单甲基-L-精氨酸（L-NMMA，10^(-4)M）增强了有内皮动脉环对EFS的收缩反应，但不影响内皮剥脱动脉的反应。L-精氨酸（10^(-4)M）逆转了L-NMMA对EFS诱导收缩的增强作用。去甲肾上腺素诱导浓度依赖性收缩，在内皮完整和内皮剥脱的动脉或用L-NMMA处理的动脉中相似。吲哚美辛（3×10^(-6)M）对EFS的收缩反应或L-NMMA对乙酰胆碱诱导舒张的抑制作用无显著影响。这些结果表明，人脑动脉对EFS的收缩反应主要受内皮细胞衍生的一氧化氮调节；尽管肾上腺素能神经似乎负责收缩，但参与一氧化氮释放的递质似乎不是去甲肾上腺素。L-NMMA在此制剂中的作用似乎是由于抑制一氧化氮的形成，而非由环氧化酶激活引起。
