INTRAARTERIAL SUBSTANCE-P MEDIATED VASODILATATION IN THE HUMAN FOREARM - PHARMACOLOGY, REPRODUCIBILITY AND TOLERABILITY

Citation
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
Citations number
29
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
03065251
Volume
43
Issue
5
Year of publication
1997
Pages
493 - 499
Database
ISI
SICI code
0306-5251(1997)43:5<493:ISMVIT>2.0.ZU;2-F
Abstract
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.