Gastrin-releasing peptide is a potent vasodilator in humans

Objectives: 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, Methods: On different occasions, 7 healthy male volunteers received brachia l artery infusions of gastrin-releasing peptide, and forearm blood flow was measured by venous occlusion plethysmography. Dose-finding studies identif ied 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. Results and Conclusions: Gastrin-releasing peptide proved to be a potent, d ose-dependent arteriolar vasodilator, The time to onset and offset of effec t was rapid, within minutes, and marked tachyphylaxis was shown, with recov ery by approximately 20 minutes. The contribution of nitric oxide to this v asodilatation was minimal. Forearm blood flow studies with the use of gastr in-releasing peptide may be usefully incorporated into the further clinical development of broad-spectrum neuropeptide growth factor antagonists.