Intra-arterial substance P mediated vasodilatation in the human forearm: pharmacology, reproducibility and tolerability.
OBJECTIVE
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.
Newby
D E
DE
Clinical Pharmacology Unit and Research Centre, University of Edinburgh, Western General Hospital, UK.
Sciberras
D G
DG
Mendel
C M
CM
Gertz
B J
BJ
Boon
N A
NA
Webb
D J
DJ
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D001916:Brachial Artery; D004305:Dose-Response Relationship, Drug; D005542:Forearm / Q000098:blood supply*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D010991:Plethysmography; D012039:Regional Blood Flow / Q000187:drug effects; D015203:Reproducibility of Results; D013373:Substance P / Q000008:administration & dosage / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D014665:Vasodilator Agents; D013373:Substance P