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

Br J Clin Pharmacol. 1997 May;43(5):493-9. doi: 10.1046/j.1365-2125.1997.00583.x.

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Pressure / drug effects
  • Brachial Artery
  • Dose-Response Relationship, Drug
  • Forearm / blood supply*
  • Heart Rate / drug effects
  • Humans
  • Infusions, Intra-Arterial
  • Male
  • Plethysmography
  • Regional Blood Flow / drug effects
  • Reproducibility of Results
  • Substance P / administration & dosage
  • Substance P / pharmacology*
  • Vasodilation / drug effects*
  • Vasodilator Agents / administration & dosage
  • Vasodilator Agents / pharmacology*

Substances

  • Vasodilator Agents
  • Substance P