Tagawa T, Mohri M, Tagawa H, Egashira K, Shimokawa H, Kuga T, Hirooka Y, Takeshita A
Research Institute of Angiocardiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
J Cardiovasc Pharmacol. 1997 Apr;29(4):546-53. doi: 10.1097/00005344-199704000-00017.
It has been shown that substance P causes endothelium-dependent vasodilation in the human coronary and forearm vessels. However, the precise mechanism whereby substance P dilates the coronary and peripheral vasculatures is unknown in humans. The aim of this study was to examine whether the vasodilator effect of substance P is mediated by nitric oxide in the human coronary and forearm vessels. Eight patients with normal coronary angiograms were studied for the measurements of coronary blood flow (intracoronary Doppler guide wire and quantitative coronary arteriography) and forearm blood flow (strain-gauge plethysmograph). Intracoronary acetylcholine (10 micrograms/min for 2 min) and substance P (30 and 90 ng/min for 2 min) increased coronary blood flow from the baseline value. Intracoronary infusion of NG-monomethyl-L-arginine (L-NMMA) at 200 mumol significantly attenuated the magnitudes of increase in coronary blood flow induced by both acetylcholine (p < 0.01) and substance P (p < 0.01). Acetylcholine (4, 8, and 16 micrograms/min for 2 min) and substance P (0.8, 1.6, and 3.2 ng/min for 2 min) also increased forearm blood flow in a dose-dependent manner. Intraarterial L-NMMA (8 mumol/min for 5 min) decreased the magnitudes of increase in forearm blood flow induced by acetylcholine (p < 0.01). L-NMMA at the same dosage decreased the increase in forearm blood flow induced by substance P, but the magnitude of the inhibitory effect of L-NMMA on blood-flow responses to substance P was significantly smaller in the forearm than in coronary vessels. It is suggested that endothelium-derived nitric oxide contributes to substance P-induced vasodilation, and that the contribution of nitric oxide to substance P-induced vasodilation is smaller in the forearm than in coronary circulation.
已表明P物质可引起人类冠状动脉和前臂血管的内皮依赖性血管舒张。然而，P物质扩张冠状动脉和外周血管系统的确切机制在人类中尚不清楚。本研究的目的是检查P物质的血管舒张作用是否由一氧化氮介导于人类冠状动脉和前臂血管。对8例冠状动脉造影正常的患者进行了冠状动脉血流（冠状动脉内多普勒导丝和定量冠状动脉造影）和前臂血流（应变片体积描记法）的测量。冠状动脉内注射乙酰胆碱（10微克/分钟，持续2分钟）和P物质（30和90纳克/分钟，持续2分钟）使冠状动脉血流从基线值增加。冠状动脉内输注200微摩尔的NG-甲基-L-精氨酸（L-NMMA）显著减弱了乙酰胆碱（p<0.01）和P物质（p<0.01）诱导的冠状动脉血流增加幅度。乙酰胆碱（4、8和16微克/分钟，持续2分钟）和P物质（0.8、1.6和3.2纳克/分钟，持续2分钟）也以剂量依赖性方式增加前臂血流。动脉内注射L-NMMA（8微摩尔/分钟，持续5分钟）降低了乙酰胆碱诱导的前臂血流增加幅度（p<0.01）。相同剂量的L-NMMA降低了P物质诱导的前臂血流增加，但L-NMMA对P物质诱导血流反应的抑制作用在前臂中比在冠状动脉中明显更小。提示内皮源性一氧化氮有助于P物质诱导的血管舒张，且一氧化氮对P物质诱导血管舒张的贡献在前臂中比在冠状动脉循环中更小。
