McEwan J R, Benjamin N, Larkin S, Fuller R W, Dollery C T, MacIntyre I
Department of Clinical Pharmacology, Royal Postgraduate Medical School, London, United Kingdom.
Circulation. 1988 May;77(5):1072-80. doi: 10.1161/01.cir.77.5.1072.
A comparison has been made of the effects of the potent vasodilating peptide calcitonin gene-related peptide (CGRP) and substance P (SP) on resistance and capacitance vessels of normal subjects. Brachial artery infusion of 1.25 to 10 pmol/min CGRP and of 0.25 to 1.5 pmol/min SP produced maximal increases in forearm blood flow (177 +/- 75% and 198 +/- 50%, respectively), as measured by venous occlusion plethysmography. The vasodilation due to CGRP was prolonged, with a half-life of biological effect of approximately 18 min, while that due to SP was of short duration, with a half-life of biological effect of approximately 15 sec. There was rapid development of tachyphylaxis to the effects of arterial infusion of SP, but not of CGRP, during a prolonged infusion at one dose. CGRP did not alter the diameter of a superficial hand vein, either at rest or when the vein was constricted by a simultaneous infusion of norepinephrine or by the single deep breath reflex. In contrast, SP caused dilatation of veins preconstricted with norepinephrine, although the effect was only transient and dose-response curves could not be constructed. The venoconstrictor response to a single deep breath was abolished by SP. Simultaneous arterial infusion of both peptides produced at least additive, and possibly synergistic, effects on forearm blood flow. We propose that both CGRP and SP have a role in the regulation of vascular smooth muscle tone.
对强效血管舒张肽降钙素基因相关肽(CGRP)和P物质(SP)对正常受试者阻力血管和容量血管的作用进行了比较。通过静脉阻断体积描记法测量,以1.25至10 pmol/分钟的速率向肱动脉输注CGRP以及以0.25至1.5 pmol/分钟的速率输注SP,可使前臂血流量产生最大增加(分别为177±75%和198±50%)。CGRP引起的血管舒张持续时间较长,生物效应半衰期约为18分钟,而SP引起的血管舒张持续时间较短,生物效应半衰期约为15秒。在以一种剂量进行长时间输注期间,对动脉输注SP的效应迅速出现快速耐受性,但对CGRP则没有。CGRP在静息时或当静脉通过同时输注去甲肾上腺素或通过单次深呼吸反射而收缩时,均不会改变浅表手部静脉的直径。相比之下,SP可使预先用去甲肾上腺素收缩的静脉扩张,尽管该效应只是短暂的,且无法构建剂量-反应曲线。SP消除了对单次深呼吸的静脉收缩反应。同时动脉输注这两种肽对前臂血流量产生至少相加的作用,甚至可能有协同作用。我们认为CGRP和SP在血管平滑肌张力的调节中均起作用。