Intra-arterial Substance P Mediated Vasodilatation in the Human Forearm: Pharmacology, Reproducibility and Tolerability

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.