De. Newby et al., INTRAARTERIAL SUBSTANCE-P MEDIATED VASODILATATION IN THE HUMAN FOREARM - PHARMACOLOGY, REPRODUCIBILITY AND TOLERABILITY, British journal of clinical pharmacology, 43(5), 1997, pp. 493-499
Aims The current studies were designed to characterize the pharmacolog
y, reproducibility and tolerability of the vasodilator response to int
ra-arterial substance P infusion in the forearm of healthy man. Method
s On different occasions, eight healthy male volunteers received brach
ial 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 venou
s occlusion plethysmography. Results Substance P induced dose-dependen
t vasodilatation in tile human forearm which had a log-linear relation
ship 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 subst
ance P. Substance P was generally well tolerated at doses of less than
or equal to 64 pmol min(-1) with no significant alteration in arteria
l blood pressure or heart rate. Skin oedema in the infused forearm and
systemic vasodilatation, manifested by facial flushing and non-infuse
d forearm vasodilatation, occurred at doses of greater than or equal t
o 16 pmol min(-1). Conclusions Forearm vasodilatation to substance P r
epresents a reproducible and useful model in the assessment of periphe
ral endothelial cell NK1 receptor function.