Warren J B, Cockcroft J R, Larkin S W, Kajekar R, Macrae A, Ghatei M A, Bloom S R
Department of Applied Pharmacology, National Heart & Lung Institute, London, U.K.
J Cardiovasc Pharmacol. 1992 Jul;20(1):83-7.
The vasodilator effect of the novel peptide pituitary adenylate cyclase activating polypeptide (PACAP) was investigated in humans. Forearm blood flow was measured in six healthy men by venous occlusion plethysmography. Infusion of PACAP into the brachial artery at 0.01, 0.1, 1, 3, and 10 pmol/min produced a dose-related increase in forearm blood flow in the cannulated arm from 2.8 +/- 0.6 to 8.6 +/- 2.4 ml/100 ml/min at the highest dose (mean +/- SEM, p less than 0.05). In a subsequent experiment, where the highest dose of PACAP was repeated after a 36 min interval, there was no tachyphylaxis of the forearm blood flow response, with the forearm blood flow increasing by 129 +/- 9% during the first infusion and 128 +/- 31% during the second infusion (N.S.). In further experiments, microvascular blood flow was measured by a laser-Doppler flow probe to compare the effects of intradermally injected PACAP, vasoactive intestinal polypeptide (VIP), and calcitonin gene-related peptide (CGRP). When injected into the skin of normal volunteers at 10(-12) to 10(-11) mol/site, each peptide caused a rapid flare lasting 2-3 min, which became erythematous after 5 min. At 10(-12) mol/site, intradermally injected PACAP and VIP caused a maximum increase in skin blood flow at 15 min of 379 +/- 96 and 307 +/- 121% (% increase above basal +/- SEM), respectively, and these responses were not significantly affected by oral aspirin (600 mg) taken 1.5 h beforehand. The vasodilation induced by PACAP at 10(-12) mol/site lasted approximately 6 h, whereas the effect of the same dose of CGRP and VIP lasted less than 2 h. These data suggest that PACAP is a potent and long-lasting vasodilator in humans.
在人体中研究了新型肽垂体腺苷酸环化酶激活多肽（PACAP）的血管舒张作用。通过静脉阻断体积描记法测量了6名健康男性的前臂血流量。以0.01、0.1、1、3和10 pmol/分钟的速率向肱动脉输注PACAP，导致插管手臂的前臂血流量出现剂量相关的增加，最高剂量时从2.8±0.6增加到8.6±2.4 ml/100 ml/分钟（平均值±标准误，p<0.05）。在随后的实验中，在间隔36分钟后重复最高剂量的PACAP，前臂血流量反应没有快速耐受性，第一次输注期间前臂血流量增加129±9%，第二次输注期间增加128±31%（无显著性差异）。在进一步的实验中，通过激光多普勒血流探头测量微血管血流量，以比较皮内注射PACAP、血管活性肠肽（VIP）和降钙素基因相关肽（CGRP）的作用。当以10^(-12)至10^(-11) mol/部位注射到正常志愿者的皮肤中时，每种肽都会引起持续2 - 3分钟的快速风团，5分钟后变为红斑。在10^(-12) mol/部位，皮内注射PACAP和VIP在15分钟时分别使皮肤血流量最大增加379±96%和307±121%（相对于基础值增加的百分比±标准误），并且这些反应不受提前1.5小时服用的口服阿司匹林（600 mg）的显著影响。10^(-12) mol/部位的PACAP诱导的血管舒张持续约6小时，而相同剂量的CGRP和VIP的作用持续不到2小时。这些数据表明，PACAP在人体中是一种强效且持久的血管舒张剂。
