Gastrin-releasing peptide is a potent vasodilator in humans.
OBJECTIVE
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 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.


CONCLUSIONS
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.
Clive
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S
ICRF Edinburgh Medical Oncology Unit and Clinical Pharmacology Unit and Research Centre, University of Edinburgh, Western General Hospital, Scotland.
Jodrell
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Webb
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D000328:Adult; D004305:Dose-Response Relationship, Drug; D005542:Forearm / Q000098:blood supply; D019886:Gastrin-Releasing Peptide / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007261:Infusions, Intra-Arterial; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology; D012039:Regional Blood Flow; D013618:Tachyphylaxis; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D014665:Vasodilator Agents; D009569:Nitric Oxide; D019886:Gastrin-Releasing Peptide