Histamine-induced vasodilatation in the human forearm vasculature

Euan A. Sandilands*, Jane Crowe, Hayley Cuthbert, Paul J. Jenkins, Neil R. Johnston, Michael Eddleston, D. Nicholas Bateman, David J. Webb

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

AimTo investigate the mechanism of action of intra-arterial histamine in the human forearm vasculature.

MethodsThree studies were conducted to assess changes in forearm blood flow (FBF) using venous occlusion plethysmography in response to intra-brachial histamine. First, the dose-response was investigated by assessing FBF throughout a dose-escalating histamine infusion. Next, histamine was infused at a constant dose to assess acute tolerance. Finally, a four way, double-blind, randomized, placebo-controlled crossover study was conducted to assess FBF response to histamine in the presence of H-1- and H-2-receptor antagonists. Flare and itch were assessed in all studies.

ResultsHistamine caused a dose-dependent increase in FBF, greatest with the highest dose (30nmolmin(-1)) infused [mean (SEM) infused arm vs. control: 26.8 (5.3) vs. 2.6mlmin(-1)100ml(-1); P <0.0001]. Dose-dependent flare and itch were demonstrated. Acute tolerance was not observed, with an increased FBF persisting throughout the infusion period. H-2-receptor antagonism significantly reduced FBF (mean (95% CI) difference from placebo at 30nmolmin(-1) histamine: -11.9mlmin(-1)100ml(-1) (-4.0, -19.8), P <0.0001) and flare (mean (95% CI) difference from placebo: -403.7cm(2) (-231.4, 576.0), P <0.0001). No reduction in FBF or flare was observed in response to the H-1-receptor antagonist. Itch was unaffected by the treatments. Histamine did not stimulate vascular release of tissue plasminogen activator or von Willebrand factor.

ConclusionHistamine causes dose-dependent vasodilatation, flare and itch in the human forearm. H-2-receptors are important in this process. Our results support further exploration of combined H-1- and H-2-receptor antagonist therapy in acute allergic syndromes.

Original languageEnglish
Pages (from-to)699-707
Number of pages9
JournalBritish Journal of Clinical Pharmacology
Volume76
Issue number5
DOIs
Publication statusPublished - 1 Nov 2013

Keywords

  • forearm blood flow
  • histamine
  • vasodilatation
  • venous occlusion plethysmography
  • PLASMINOGEN-ACTIVATOR RELEASE
  • HUMAN-ENDOTHELIAL CELLS
  • N-ACETYLCYSTEINE
  • H-1
  • RECEPTORS
  • RESPONSES
  • ANTAGONISTS
  • H-2-RECEPTORS
  • STIMULATION
  • INVOLVEMENT

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