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

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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