Intra‐arterial substance P mediated vasodilatation in the human forearm: pharmacology, reproducibility and tolerability

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Abstract
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 ≤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 ≥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.

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