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

D E Newby, D G Sciberras, C M Mendel, B J Gertz, N A Boon, D J Webb

Research output: Contribution to journalArticlepeer-review

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 < 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.

Original languageEnglish
Pages (from-to)493-9
Number of pages7
JournalBritish Journal of Clinical Pharmacology
Volume43
Issue number5
Publication statusPublished - May 1997

Keywords

  • Adult
  • Blood Pressure
  • Brachial Artery
  • Dose-Response Relationship, Drug
  • Forearm
  • Heart Rate
  • Humans
  • Infusions, Intra-Arterial
  • Male
  • Plethysmography
  • Regional Blood Flow
  • Reproducibility of Results
  • Substance P
  • Vasodilation
  • Vasodilator Agents

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