Clive S, Jodrell D, Webb D
ICRF Edinburgh Medical Oncology Unit and Clinical Pharmacology Unit and Research Centre, University of Edinburgh, Western General Hospital, Scotland.
Clin Pharmacol Ther. 2001 Apr;69(4):252-9. doi: 10.1067/mcp.2001.114888.
Our objective was to characterize the local vascular effects of gastrin-releasing peptide in forearm resistance vessels as a biomarker to aid the clinical development of broad-spectrum neuropeptide antagonists as anticancer agents.
On different occasions, 7 healthy male volunteers received brachial artery infusions of gastrin-releasing peptide, and forearm blood flow was measured by venous occlusion plethysmography. Dose-finding studies identified a range of pharmacologically active doses of gastrin-releasing peptide (3 to 450 pmol/min) for use in dose response and tachyphylaxis studies. The nitric oxide clamp method was used for the assessment of the contribution of nitric oxide to the vasodilatory effect shown.
Gastrin-releasing peptide proved to be a potent, dose-dependent arteriolar vasodilator. The time to onset and offset of effect was rapid, within minutes, and marked tachyphylaxis was shown, with recovery by approximately 20 minutes. The contribution of nitric oxide to this vasodilatation was minimal. Forearm blood flow studies with the use of gastrin-releasing peptide may be usefully incorporated into the further clinical development of broad-spectrum neuropeptide growth factor antagonists.
我们的目标是将胃泌素释放肽在前臂阻力血管中的局部血管效应作为一种生物标志物进行表征，以辅助广谱神经肽拮抗剂作为抗癌药物的临床开发。
在不同时间，7名健康男性志愿者接受肱动脉输注胃泌素释放肽，并通过静脉阻断体积描记法测量前臂血流量。剂量探索研究确定了一系列用于剂量反应和快速耐受研究的具有药理活性的胃泌素释放肽剂量（3至450皮摩尔/分钟）。采用一氧化氮钳夹法评估一氧化氮对所示血管舒张作用的贡献。
胃泌素释放肽被证明是一种强效的、剂量依赖性的小动脉血管舒张剂。效应的起效和消退时间很快，在数分钟内，并且显示出明显的快速耐受，约20分钟后恢复。一氧化氮对这种血管舒张的贡献最小。使用胃泌素释放肽进行的前臂血流量研究可能有助于纳入广谱神经肽生长因子拮抗剂的进一步临床开发。
