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AIMS: The current studies were designed to characterize the pharmacology, reproducibility and tolerability of the vasodilator response to intra-arterial substance P infusion in the forearm of healthy man. METHODS: On different occasions, eight healthy male volunteers received brachial artery infusions of substance P at doubling doses ranging from 0.5 to 128 pmol min(-1). Blood flow was measured in both arms using venous occlusion plethysmography. RESULTS: Substance P induced dose-dependent vasodilatation in the human forearm which had a log-linear relationship to dose. At doses of 1-8 pmol min(-1), mean responses were highly reproducible both within and between days. There were no differences between responses to discontinuous doses and continuous doses of substance P. Substance P was generally well tolerated at doses of < or = 64 pmol min(-1) with no significant alteration in arterial blood pressure or heart rate. Skin oedema in the infused forearm and systemic vasodilatation, manifested by facial flushing and non-infused forearm vasodilatation, occurred at doses of > or = 16 pmol min(-1). CONCLUSIONS: Forearm vasodilatation to substance P represents a reproducible and useful model in the assessment of peripheral endothelial cell NK1 receptor function.

Original publication

DOI

10.1046/j.1365-2125.1997.00583.x

Type

Journal article

Journal

Br j clin pharmacol

Publication Date

05/1997

Volume

43

Pages

493 - 499

Keywords

Adult, Blood Pressure, Brachial Artery, Dose-Response Relationship, Drug, Forearm, Heart Rate, Humans, Infusions, Intra-Arterial, Male, Plethysmography, Regional Blood Flow, Reproducibility of Results, Substance P, Vasodilation, Vasodilator Agents